Bibliography, page 4

1. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.computation_on_this_corpus
   Random-sample read of 50 same-source counter-evidence notes against a pre-fixed four-way taxonomy

   king, Oncofusion knowledge graph, cycle 66 · analyses/counter-note-same-source-taxonomy/sample.py 2026
   used by The standing worry about same-source counter-evidence, read at n=50: 84% are the author's own caveat or a point of logic, 16% could have cited independent literature, and none of fifty is unsupported
2. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
   Ensembl REST canonical MEN1 CDS (ENST00000450708) and UniProt O00255, translated and checked, computed by analyses/q204-failure-mode-atlas/escape_reachability.py on 2026-10-14

   · Ensembl / UniProt 2026
   used by The ten reported menin-inhibitor escape substitutions are each one nucleotide change from the MEN1 sequence - which the sources could not have shown otherwise - so the useful outputs are a 25-variant validation panel and a burden threshold, not the headline
3. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
   absence-gse210480-processed-tracks-are-1-kb-binned and data/symbol-collisions.json row 'A BINNED coverage track answers a finer query without error, and the answer is plausible', read 2026-09-22, together with this cycle's domain-width measurement

   · Iqbal Lab oncofusion knowledge graph 2026
   used by The third resolution trap in three cycles: an ENRICHED-domain BED has a median domain of 13-17 kb and a per-SAMPLE bin size, so 'the GAPDH promoter is inside an H3K9me3 domain' is true in the file and means nothing about the promoter
4. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.dataset
   Affinity purification of the AF4 and AF4-MLL complexes, as reported in this knowledge graph's complex-af4-mll-assembles-a-sixteen-component-elongation-machine entry: the AF4-MLL complex comprises at least 16 constituents including P-TEFb kinase, and AF4-MLL enhances calcitriol-dependent ALOX5 transcript elongation in a flavopiridol-sensitive manner while the direct MLL-AF4 product has no effect on elongation

   Oncofusion Knowledge Graph, reciprocal-product beat · Internal knowledge graph entry 2026
   used by The two t(4;11) products split AFF1 exactly at the P-TEFb-binding module, and the elongation half goes to the reciprocal
5. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis
   analyses/which-b-all-cohorts-can-test-arid1a/{recon.py, run.py, join.py, recon.json, results.json, join_results.json, donor_overlap_check.json, kmt2a_variable_by_cohort.json, all_stjude_2013_both_variables.json}, this repository; cBioPortal API queried 2026-09-23

   Oncofusion knowledge graph, coordinator · internal analysis, reproducible from the repository 2026
   used by The two TARGET B-ALL studies in cBioPortal are 868 of the same patients assayed twice, so joining them DOES answer the question I had just written off as unanswerable: all four ARID1A-mutant B-ALL patients are definitively KMT2A-negative, three of them with truncating calls. The answer is zero of three - and at a 2.7% KMT2A-positive rate an empty overlap has probability 0.92, so it is an upper bound and not a finding
6. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
   DOT1L-mediated H3K79me2 directs B-cell repertoire establishment, marginal zone development, and germinal center function (GSE306634)

   GEO submitters · NCBI Gene Expression Omnibus 2026
   used by The unnamed Cre is Mb1-Cre, which acts at the pro-B stage: the one resolution in this beat that lands on the right cell
7. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
   UniProtKB entries P13196, P13716, P10746 and P48200: primary gene names and recommended protein names

   UniProt Consortium · UniProtKB 2026
   used by The whole protein-coding genome: menin is still first, and a metabolic pathway appears (run)
8. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
   concept-wdr5-what-is-established-for-wild-type-kmt2a-and-what-for-the-fusion (this corpus)

   · Oncofusion Knowledge Graph 2026
   used by The WRAD degron absence survives, and the reason is worth more than the verdict: a 3.7 nM chemical degron of WDR5 with 2-hour kinetics already exists IN MV4;11, and it still cannot see the fusion
9. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
   scripts/is-symbol-covered.py WDR5, oncofusion-knowledge-graph, run 2026-09-24

   · this project 2026
   used by The WRAD degron absence survives, and the reason is worth more than the verdict: a 3.7 nM chemical degron of WDR5 with 2-hour kinetics already exists IN MV4;11, and it still cannot see the fusion
10. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.analysis
    analyses/can-this-corpus-say-which-readout-an-occupancy-claim-rests-on/run.py and results.json, this repository, computed 2026-09-24 against the committed node files

    Oncofusion knowledge graph, coordinator · internal analysis, reproducible from the repository 2026
    used by This corpus argued from the literature that intersecting fusion peaks with partner peaks cannot attribute occupancy, and eighty cycles later a beat measured that partner antibody sitting at the negative control in primary patient samples - two independent derivations from the same paper, with no edge between them and one wrong premise
11. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
    analyses/q166-the-akap95-dpy30-axis/akap-corpus-92-titles.json - complete efetch of all 92 records matching AKAP8[tiab] OR AKAP95[tiab], with titles and years, 2026-09-24

    · this project 2026
    used by This graph recorded 'nobody has looked at AKAP95 in any KMT2A fusion' one cycle before reading the 2026 paper that did - KMT2A returns 0, MLL returns 2, and every cell-line token returns 0 because cell lines live in figures
12. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41262054
    Acute myeloid leukemia with t(10;17)(p15;q21)/ ZMYND11::MBTD1: a subtype with minimal differentiation, CD7/CD56 expression, and generally poor outcomes in adults.

    Wei Q, Pemmaraju N, Wang SA, Hu S, et al. · Haematologica 2026
    used by Three blots and one drug curve: does the ZMYND11::MBTD1 fusion protein still bind KMT2A, and does a menin inhibitor work in a leukaemia with no KMT2A rearrangement, ZMYND11 (BS69) - an H3.3K36me3 reader that restrains elongation, is itself the 5' partner of a chromatin-hijacking AML fusion driving HOXA/MEIS1/MYB, and whose promoter is the third-strongest MLL1-N bin in RS4;11, ZMYND11::MBTD1 is the KMT2A-fusion architecture assembled from different parts - and the part it throws away is a direct physical brake on KMT2A itself, ZMYND11::MBTD1, t(10;17)(p15;q21) - a chromatin reader welded to the NuA4/TIP60 acetyltransferase, maintaining Hoxa/Meis1/Myb/Myc/Sox4 in AML: the KMT2A-fusion architecture built from different parts
13. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    PubMed E-utilities esearch, counted-absence query set for XPO1 chromatin occupancy in KMT2A-rearranged leukaemia

    Oncofusion Knowledge Graph project (Q61-export-axis) · NCBI E-utilities 2026
    used by Three measurements the export axis needs and nobody has published: XPO1 occupancy in KMT2A-r, H3K79 under an XPO1 inhibitor, and CRM1 occupancy under a menin inhibitor
14. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    Oncofusion KG live query, 2026-09-24: NCBI E-utilities elink dbfrom=gene db=medgen over the four human AFF genes, with esummary of each returned concept

    Q187-the-sec-family-and-yeats-selectivity · this project 2026
    used by Three of the four AFF scaffolds have a named human Mendelian syndrome and the index fusion's partner has none — a 0/4 that is a fact about AFF1 and not about how hard anyone has looked
15. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysis
    Junction peptides and masses for all three UniProt-annotated recurrent KMT2A breakpoints in KMT2A::AFF1

    · Oncofusion knowledge graph (internal analysis) 2026
    used by Three recurrent breakpoints give three junction peptides - and the one nobody uses needs no missed cleavage at all
16. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB entry Q6ZNK6 (TIFAB_HUMAN), TRAF-interacting protein with FHA domain-containing protein B

    UniProt Consortium · UniProt 2026
    used by TIFAB — a 161-residue NF-kB adaptor-layer protein with TWO direct KMT2A-fusion papers, which is more disease-specific evidence than any receptor or TRAF in this beat has
17. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    UniProtKB Q6ZNK6 (TIFAB) SUBCELLULAR LOCATION comment, fetched 2026-09-21

    · UniProt Consortium 2026
    used by TIFAB — a 161-residue NF-kB adaptor-layer protein with TWO direct KMT2A-fusion papers, which is more disease-specific evidence than any receptor or TRAF in this beat has
18. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    PubMed E-utilities esearch, 2026-09-21. all four hits retrieved by efetch and read before the absence was recorded; the literature is small enough that the bound is close to exhaustive for titles and abstracts

    · NCBI PubMed 2026
    used by TIFAB — a 161-residue NF-kB adaptor-layer protein with TWO direct KMT2A-fusion papers, which is more disease-specific evidence than any receptor or TRAF in this beat has
19. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB Q9BYE2 (TMPSD_HUMAN) - Transmembrane protease serine 13 (MSPL / mosaic serine protease); canonical isoform 1, 586 aa

    UniProt Consortium · UniProtKB 2026
    used by TMPRSS13 (MSPL) - a cell-surface serine protease fused in frame to KMT2A exon 20, the clearest NOT-APPLICABLE epigenetics call of the seven, and a symbol whose approved form has a third of its alias's recall
20. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
    RefSeq NM_001077263.3 - Homo sapiens transmembrane serine protease 13 (TMPRSS13), transcript variant 1, mRNA - NP_001070731.1, 567 aa

    NCBI RefSeq · NCBI Nucleotide 2026
    used by TMPRSS13 (MSPL) - a cell-surface serine protease fused in frame to KMT2A exon 20, the clearest NOT-APPLICABLE epigenetics call of the seven, and a symbol whose approved form has a third of its alias's recall
21. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.dataset
    DepMap CRISPR (Chronos) gene-effect scan of 11 KMT2A-rearranged versus 43 other leukaemia lines (this project's own scan)

    Broad Institute DepMap; joined locally from analyses/depmap-kmt2a-selective-scan-full · analyses/depmap-kmt2a-selective-scan-full 2026
    used by TMPRSS13 (MSPL) - a cell-surface serine protease fused in frame to KMT2A exon 20, the clearest NOT-APPLICABLE epigenetics call of the seven, and a symbol whose approved form has a third of its alias's recall
22. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB entry P01375 (TNFA_HUMAN), Tumor necrosis factor

    UniProt Consortium · UniProt 2026
    used by TNF — the only NF-kB-activating ligand with real KMT2A::AFF1 B-ALL evidence, and the evidence says the blasts are RESISTANT to it
23. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB P01375 (TNFA_HUMAN), SUBCELLULAR LOCATION comments for the membrane form, the soluble form and the C-domain chains with evidence codes and the topology feature table, fetched live 2026-09-22

    UniProt Consortium · Databases 2026
    used by TNF — the only NF-kB-activating ligand with real KMT2A::AFF1 B-ALL evidence, and the evidence says the blasts are RESISTANT to it
24. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB P11388 (TOP2A_HUMAN), DNA topoisomerase 2-alpha, 1531 aa, primary gene name TOP2A

    · UniProt Consortium 2026
    used by TOP2A - the proliferation isoform, the one the drugs are actually measured against, and the only one with a germline association in this disease
25. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41663397
    MYC modulates TOP2A diffusion to promote substrate detection and activity.

    Cameron DP, et al. · Nat Commun 2026;17 2026
    used by TOP2A - the proliferation isoform, the one the drugs are actually measured against, and the only one with a germline association in this disease
26. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB Q02880 (TOP2B_HUMAN), DNA topoisomerase 2-beta, 1626 aa, primary gene name TOP2B

    · UniProt Consortium 2026
    used by TOP2B - the isoform most etoposide-induced KMT2A breaks depend on, resolved genetically and not resolvable pharmacologically
27. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    IntAct REST findInteractions/Q92547 (TOPBP1), 85 records, 1 against a core bait; and findInteractions/17913746, 17 records; fetched 2026-09-21

    · EMBL-EBI IntAct 2026
    used by TOPBP1 - a real KMT2A contact that no abstract-level query can see, because it is a control panel in a paper about a different protein
28. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    PubMed esearch: TOPBP1[tiab] AND (MLL OR KMT2A)[tiab] = 0; TOPBP1[tiab] AND leukemia[tiab] = 4; run 2026-09-21

    · NCBI PubMed 2026
    used by TOPBP1 - a real KMT2A contact that no abstract-level query can see, because it is a control panel in a paper about a different protein
29. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB Q92547 (TOPB1_HUMAN) SUBCELLULAR LOCATION comment, fetched 2026-09-21

    · UniProt Consortium 2026
    used by TOPBP1 - a real KMT2A contact that no abstract-level query can see, because it is a control panel in a paper about a different protein
30. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 42152682
    Treacle-dependent TOPBP1 condensation regulates the nucleolar DNA damage response.

    · Nucleic Acids Res 2026
    used by TOPBP1 - a real KMT2A contact that no abstract-level query can see, because it is a control panel in a paper about a different protein
31. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 42104014
    TopBP1 orchestrates PU.1-IRF8 transcriptional programming of dendritic cell differentiation and Flt3L-driven tumor immunity.

    · Exp Mol Med 2026
    used by TOPBP1 - a real KMT2A contact that no abstract-level query can see, because it is a control panel in a paper about a different protein
32. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
    Human Protein Atlas v25.1, subcellular (immunofluorescence) and Blood Atlas records for TOPBP1, fetched 2026-09-21

    · Human Protein Atlas 2026
    used by TOPBP1 - a real KMT2A contact that no abstract-level query can see, because it is a control panel in a paper about a different protein
33. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB P04637 (P53_HUMAN) - SUBCELLULAR LOCATION comment blocks with evidence codes, including the seven isoform-scoped comments

    · UniProt Consortium 2026
    used by TP53 - named in 84 entries of this graph, absent from the index genome study of the disease, and four different things depending on when you look
34. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.reviewPMID 42251692
    Menin inhibitors for patients with relapsed/refractory acute myeloid leukemia (AML): a systematic review and meta-analysis.

    Alhajahjeh A, Beke KE, Grimshaw AA, et al. · Leuk Lymphoma 2026
    used by TP53 inactivation and the apoptotic threshold — the drug still switches the program off, and the cell still does not die
35. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB Q12888 (TP53B_HUMAN), TP53-binding protein 1, 1972 aa, primary gene name TP53BP1

    · UniProt Consortium 2026
    used by TP53BP1 (53BP1) - the end-protection factor that decides between the two repair routes, reachable only under the wrong symbol
36. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
    PubMed esearch, db=pubmed, terms '(MLL OR KMT2A) AND TP53BP1' (count 0) and '(MLL OR KMT2A) AND 53BP1' (count 5), run 2026-09-20; querytranslations read and free of [UID] artefact

    · NCBI PubMed 2026
    used by TP53BP1 (53BP1) - the end-protection factor that decides between the two repair routes, reachable only under the wrong symbol
37. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.database
    IntAct molecular interaction database, PSICQUIC MITAB 2.7, query id:Q12933 AND id:Q9UHB7, 3 rows retrieved 2026-09-21

    · IntAct (EMBL-EBI) 2026
    used by TRAF2 - a cytoplasmic NF-kB brake reported as an AFF4 two-hybrid hit, 97 partners in the screen that found it, and the live instance of the brief's own accession trap
38. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB entries Q12933 (TRAF2_HUMAN) and Q9UHB7 (AFF4_HUMAN), subcellular location and function comments with evidence codes

    · UniProtKB/Swiss-Prot 2026
    used by TRAF2 - a cytoplasmic NF-kB brake reported as an AFF4 two-hybrid hit, 97 partners in the screen that found it, and the live instance of the brief's own accession trap, Zero of eight unwritten AFF4/MEN1 partners has an experimentally coded nuclear localisation, and the two that are called nuclear are called it by inference
39. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    PubMed counted-absence search for TRAF2 against MLL and KMT2A, run 2026-09-21

    · PubMed (NCBI) 2026
    used by TRAF2 - a cytoplasmic NF-kB brake reported as an AFF4 two-hybrid hit, 97 partners in the screen that found it, and the live instance of the brief's own accession trap
40. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProt REST search, gene_exact:TRAF2 AND organism_id:9606 AND reviewed:true, fields accession,id,gene_primary,gene_synonym,protein_name,length, run 2026-09-21

    · UniProtKB/Swiss-Prot 2026
    used by TRAF2 - a cytoplasmic NF-kB brake reported as an AFF4 two-hybrid hit, 97 partners in the screen that found it, and the live instance of the brief's own accession trap
41. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41855552
    Inhibition of USP7 Destabilizes the Noncanonical PRC1.1 Complex and Induces Neuroblastoma Differentiation.

    Cmarik EA, Wahi A, Chandekar SS, Otchere SK, Sturgis JE, Salhotra S, et al. · Mol Cancer Res 2026
    used by TRIM27 - the E3 ligase inside PRC1.1 that USP7 spends its time undoing, and the worst UniProt localisation record this graph has audited, USP7 - the enzyme that holds PRC1.1 together, and the only pharmacological handle on this complex that exists today
42. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB reviewed human record for TRIM27 (P14373), resolved by gene_exact:TRIM27 AND organism_id:9606 AND reviewed:true with gene_primary and length read back

    UniProt Consortium · UniProtKB 2026
    used by TRIM27 - the E3 ligase inside PRC1.1 that USP7 spends its time undoing, and the worst UniProt localisation record this graph has audited
43. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB P14373 (TRI27_HUMAN), SUBCELLULAR LOCATION comment with every location-to-citation mapping read back from the raw JSON, fetched live 2026-09-22

    UniProt Consortium · Databases 2026
    used by TRIM27 - the E3 ligase inside PRC1.1 that USP7 spends its time undoing, and the worst UniProt localisation record this graph has audited
44. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB Q9Y4A5 (TRRAP_HUMAN), SUBCELLULAR LOCATION comment with evidence codes and sources plus the feature table including the bipartite NLS motif, fetched live 2026-09-22

    UniProt Consortium · Databases 2026
    used by TRRAP — a 3,859-residue DotCom subunit that every cell needs and no KMT2A cell needs more
45. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    Europe PMC REST: PMC10522653 fullTextXML (ANZCHOG infant ALL cohort, Table 1)

    · EMBL-EBI 2026
    used by Two cohorts, a hundred infants each, and opposite answers on which sex does worse
46. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.analysis
    Cross-entry audit of sex-effect claims in the Oncofusion knowledge graph (coordinator, cycle 50)

    · Oncofusion knowledge graph (internal audit) 2026
    used by Two cohorts, a hundred infants each, and opposite answers on which sex does worse
47. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    pybigtools 0.3.0 - observed behaviour when converting six GEO HOMER bedGraphs to bigWig on 2026-09-22 (KeyError on chrUn_GL000219v1; ValueError 'Invalid file path. Writing does not support urls' on a C: path, resolved with the //?/ extended-length form)

    pybigtools maintainers · PyPI / bigtools 2026
    used by Two coupled traps in one conversion: pybigtools writes only the chromosomes the input actually touched, so a scaffold in your query set raises KeyError on one track and not another - and when the scaffolds were dropped to fix it, 71 of 59,892 anchors (0.12%) turned out to carry enough of the top signal to HALVE a control's numerator
48. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
    data/symbol-collisions.json, oncofusion-knowledge-graph, read 2026-09-24

    · this project 2026
    used by Two new contaminated tokens for the registry - p75 (12 of 27 hits are TNF receptor) and AF-10 (an IL-6-responsive B cell line) - and SEM firing a second time, in a different query, one cycle after being written down
49. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    ana-testing-the-refusals-instead-of-the-gaps-overturned-the-first-one-tried (this corpus)

    · Oncofusion Knowledge Graph 2026
    used by Two new contaminated tokens for the registry - p75 (12 of 27 hits are TNF receptor) and AF-10 (an IL-6-responsive B cell line) - and SEM firing a second time, in a different query, one cycle after being written down
50. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    NCBI E-utilities esearch, db=pubmed, run 2026-09-24; probe-log.jsonl record label ledgf/ibd-mll-ligand, all 27 titles stored

    · NCBI PubMed 2026
    used by Two new contaminated tokens for the registry - p75 (12 of 27 hits are TNF receptor) and AF-10 (an IL-6-responsive B cell line) - and SEM firing a second time, in a different query, one cycle after being written down
51. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB Q9H4G0 (E41L1_HUMAN) features, comments, subcellular-location evidence and tissue specificity; HGNC:3378 prev_symbol null and alias_symbol [KIAA0338, 4.1N] via rest.genenames.org; retrieved 2026-09-22

    · UniProt Consortium / HGNC 2026
    used by Two of seven interactome read-queue partners should not get a gene entry, and the reasons are a pseudokinase with no nuclear pool and a membrane-skeleton protein whose two leukaemia hits are a gene-name artefact
52. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset
    analyses/depmap-kmt2a-selective-scan-full/results.json - 17,728 protein-coding genes, 11 Cellosaurus-annotated KMT2A-rearranged versus 43 other leukaemia lines, computed 2026-09-19

    · DepMap (Broad Institute), via this repository's scan 2026
    used by Two of seven interactome read-queue partners should not get a gene entry, and the reasons are a pseudokinase with no nuclear pool and a membrane-skeleton protein whose two leukaemia hits are a gene-name artefact
53. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    IntAct REST findInteractions/Q8NCB2 (267 indexed) and /Q9H4G0 (176 indexed), filtered to the six core-scaffold plus ELL/MLLT1/MLLT3/MLLT10 accessions, with ac, uniqueIdA/B, experimentalRole, detectionMethod, hostOrganism and publicationPubmedIdentifier read per row; cross-checked against IntAct PSICQUIC MITAB, which shows uniprotkb:Q8NCB2-2 in the BioPlex 2.0 rows; retrieved 2026-09-22

    · IntAct molecular interaction database (EMBL-EBI) 2026
    used by Two of seven interactome read-queue partners should not get a gene entry, and the reasons are a pseudokinase with no nuclear pool and a membrane-skeleton protein whose two leukaemia hits are a gene-name artefact
54. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    NCBI E-utilities esearch, db=pubmed, querytranslation read back from every response, with PubMed publication types read from efetch for PMID 34141456; run 2026-09-22

    · NCBI PubMed 2026
    used by Two of seven interactome read-queue partners should not get a gene entry, and the reasons are a pseudokinase with no nuclear pool and a membrane-skeleton protein whose two leukaemia hits are a gene-name artefact
55. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 41481226
    CRM1 inhibits NPAT condensation and histone locus body formation via a competitive occupation strategy.

    Cong XX, et al. · Journal of Cell Biology 2026
    used by Two pools of one protein: the chromatin-bound XPO1 that matters here has never been separated biochemically from the soluble export machine
56. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysis
    verify-accessions.py - UniProt accession verification across the graph, widened to entries carrying an accession without an asserted gene symbol

    · Oncofusion knowledge graph (internal tooling) 2026
    used by Two quality checkers audited: one was skipping a quarter of its input, the other did not exist and failed its own defining case twice before it worked
57. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysis
    check-quoted-retractions.py - finding retracted wording that is still asserted elsewhere in the same entry

    · Oncofusion knowledge graph (internal tooling) 2026
    used by Two quality checkers audited: one was skipping a quarter of its input, the other did not exist and failed its own defining case twice before it worked
58. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    PSI-MI ontology terms MI:1060, MI:1061, MI:0914, MI:0915, MI:0407, MI:2364 and MI:0403, labels and definitions read back from the EBI Ontology Lookup Service on 2026-09-21

    · EMBL-EBI Ontology Lookup Service 4 / HUPO PSI-MI controlled vocabulary 2026
    used by Two thirds of the curated interactome of this project's six core proteins is spoke-expanded - and the pairs this graph chose to write are significantly better than the ones it did not, What a curated interaction row actually claims: spoke expansion, and the ladder from 'was in the same tube' to 'touches'
59. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    RCSB PDB entry and polymer-entity records for 3U88, 5JW9, 6PWV, 2MSR, 2MTN and 6EMQ, each entity's UniProt mapping read back individually, fetched 2026-09-21

    · RCSB Protein Data Bank 2026
    used by Two thirds of the curated interactome of this project's six core proteins is spoke-expanded - and the pairs this graph chose to write are significantly better than the ones it did not
60. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis
    system-of-record: species, lineage and model markers inferred from claim and caveat text across all evidence items

    · Oncofusion knowledge graph (internal analysis) 2026
    used by Two-thirds of the load-bearing evidence names no lineage, which is why this graph cannot audit its own commonest failure
61. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysis
    interactome-bait-versus-prey: experimental-role grading of core-complex interaction partners from IntAct MITAB 2.7

    · Oncofusion knowledge graph (internal analysis) 2026
    used by Two-thirds of this graph's core-complex interaction evidence comes from experiments where our protein was not the bait, and LEDGF has one bait-supported partner out of thirty-six
62. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    Cellosaurus CVCL_0007 (U-937): adult acute monocytic leukaemia, male, lost chromosome Y, flagged Problematic cell line - partially contaminated, some ATCC stocks cross-contaminated by K-562

    · Cellosaurus (SIB) 2026
    used by U-937 (CVCL_0007) - the single line carrying this graph's menin-independence argument, and it is adult, monocytic, historically contaminated, and exists as two variants nobody here distinguishes
63. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    IntAct molecular interaction database (EMBL-EBI), PSICQUIC tab27 record for id:Q01081 AND id:O75475

    2026
    used by U2AF1 - the 3' splice-site recognition factor, a speckle protein whose BioID neighbourhood contains LEDGF
64. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB Q01081 (U2AF1_HUMAN)

    2026
    used by U2AF1 - the 3' splice-site recognition factor, a speckle protein whose BioID neighbourhood contains LEDGF
65. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    PubMed counted absence search for UBE2T against KMT2A/MLL, run 2026-09-20 with aliases and title-checked

    · PubMed (NCBI) 2026
    used by UBE2T — E2; rank 33 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all
66. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB Q9NPG3 (UBN1_HUMAN), Ubinuclein-1, 1134 aa

    · UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
    used by UBN1 - the subunit that decides the HIRA complex is carrying H3.3 and not H3.1, by reading a single glycine
67. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    ChEMBL molecule records CHEMBL2441082 and CHEMBL1231795, synonym lists and molecular properties read back directly

    · EMBL-EBI ChEMBL 2026
    used by UNC0642 - the G9a/GLP chemical probe that abolished doxorubicin-induced Kmt2a copy gain in mice, and the one intervention in this beat that has been given to an animal
68. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    HGNC:12313 JMJD1C, jumonji domain containing 1C (alias KDM3C; previous symbol TRIP8; UniProt Q15652)

    · HUGO Gene Nomenclature Committee 2026
    used by Under EPZ5676 the canonical KMT2A-fusion targets look like they lose H3K79me2 far more than the genome (p=0.017 and p=0.0004), and against a baseline-matched null the entire effect vanishes (p=0.34 and p=0.22) - eight of the ten are simply top-decile genes
69. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.analysis
    USP1 module membership: does its cross-line dependency profile track the Fanconi monoubiquitination module or the ID1 axis?

    · Oncofusion knowledge graph (internal analysis) 2026
    used by USP1 does not behave like part of the Fanconi module, and does not track ID1 either
70. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysis
    USP1 module membership, lineage-split: haematological against other lineages

    · Oncofusion knowledge graph (internal analysis) 2026
    used by USP1 does not behave like part of the Fanconi module, and does not track ID1 either
71. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB reviewed human record for USP7 (Q93009), resolved by gene_exact:USP7 AND organism_id:9606 AND reviewed:true with gene_primary and length read back

    UniProt Consortium · UniProtKB 2026
    used by USP7 - the enzyme that holds PRC1.1 together, and the only pharmacological handle on this complex that exists today
72. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    PubMed E-utilities esearch counts for KMT2A partner symbol and alias queries, run 2026-09-19

    National Center for Biotechnology Information (NCBI), PubMed · PubMed (NCBI E-utilities) 2026
    used by USP8 (UBPY) - the second deubiquitinase KMT2A partner, three patients, same UCH logic
73. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
    NCBI PubMed esearch, bounded-absence query (counted negative)

    · NCBI E-utilities 2026
    used by UTP14A (Q9BVJ6) - an SSU processome component that binds and destabilises p53, in four MLL-fusion interactomes but NOT the index fusion's and below the screen threshold
74. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    IntAct molecular interaction database, PSICQUIC MITAB 2.7, query id:Q9Y5J1 AND id:Q03164 and query pubid:15199122, retrieved 2026-09-21

    · IntAct (EMBL-EBI) 2026
    used by UTP18 is not a KMT2A partner - it is WDR5, mis-curated into IntAct from the founding paper, and it manufactured the only KMT2A-bait gap in the interactome recount
75. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    IntAct molecular interaction database, PSICQUIC MITAB 2.7, query pubid:15199122, 13 rows retrieved 2026-09-21

    · IntAct (EMBL-EBI) 2026
    used by UTP18 is not a KMT2A partner - it is WDR5, mis-curated into IntAct from the founding paper, and it manufactured the only KMT2A-bait gap in the interactome recount
76. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    IntAct molecular interaction database, PSICQUIC MITAB 2.7, query id:P61964 AND id:Q03164, 3 rows retrieved 2026-09-21

    · IntAct (EMBL-EBI) 2026
    used by UTP18 is not a KMT2A partner - it is WDR5, mis-curated into IntAct from the founding paper, and it manufactured the only KMT2A-bait gap in the interactome recount
77. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB entries Q9Y5J1 (UTP18_HUMAN) and P61964 (WDR5_HUMAN)

    · UniProtKB/Swiss-Prot 2026
    used by UTP18 is not a KMT2A partner - it is WDR5, mis-curated into IntAct from the founding paper, and it manufactured the only KMT2A-bait gap in the interactome recount
78. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    PubMed esearch counts for valemetostat queries, run 2026-09-20

    · NCBI PubMed 2026
    used by Valemetostat - an approved dual EZH1/EZH2 inhibitor that has already worked in an MLL-AF4 xenograft, in a disease nobody has enrolled it in
79. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis
    analyses/would-the-year-check-have-caught-the-known-failures/run.py and results.json, this repository, computed 2026-09-24 against the committed node files with each identifier's year resolved live from PubMed esummary or Crossref

    Oncofusion knowledge graph, coordinator · internal analysis, reproducible from the repository 2026
    used by Validating the wrong-paper year check against this project's own recorded identifier errors - 16 of 23 would have been flagged, 7 would have passed silently on a shared year, and the figure is biased optimistic because every pair in the set is an error somebody caught
80. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB P19320 (VCAM1_HUMAN)

    · UniProtKB 2026
    used by VCAM1 - the stromal counter-receptor for VLA-4, and in MLL-fusion AML its UPREGULATION is anti-leukaemic, which is the opposite of the expected sign
81. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    Ensembl REST (KMT2A ENST00000534358; VIM ENST00000544301) and UniProtKB (Q03164; P08670) records, exon boundaries intersected with the feature tables

    Ensembl (EMBL-EBI); UniProt Consortium · Ensembl REST / UniProtKB 2026
    used by VIM::KMT2A - the one KMT2A rearrangement that keeps the SET domain and still throws away the menin-binding exon, Vimentin domain coordinates (P08670) - so the VIM::KMT2A breakpoint can actually be drawn
82. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB P08670 (VIME_HUMAN), Vimentin, feature table and sequence

    UniProt Consortium · UniProtKB 2026
    used by Vimentin domain coordinates (P08670) - so the VIM::KMT2A breakpoint can actually be drawn
83. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
    Total Therapy for Infants With Acute Lymphoblastic Leukemia (ALL) I

    St. Jude Children's Research Hospital · ClinicalTrials.gov API v2, retrieved 2026-09-20 via the raw API per this project's registry rule 2026
    used by Vorinostat (SAHA) - the only HDAC inhibitor given to newly diagnosed infants with ALL, in a 50-patient trial whose endpoint was tolerability and which reported four treatment-related deaths, all infectious
84. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB Q9BTA9 (WAC_HUMAN) and Q924H7 (WAC_MOUSE), SUBCELLULAR LOCATION comments with evidence codes and sources, both fetched live 2026-09-22

    UniProt Consortium · Databases 2026
    used by WAC — the adaptor that hands RNF20/RNF40 to RNA polymerase II, and the only member of this axis whose knockdown alone killed MLL-rearranged ALL cells
85. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    UniProtKB - Q9BV38 (WDR18_HUMAN), WD repeat-containing protein 18

    · UniProt Knowledgebase 2026
    used by WDR18 (Q9BV38) - the Rix1/PELP1-TEX10-WDR18 60S maturation subunit, in five MLL-fusion interactomes but NOT the index fusion's, and the block's only member whose nucleolar partitioning is SUMO-controlled
86. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    ChEMBL database version 34, target CHEMBL1075317 (WD repeat-containing protein 5): target_search, get_bioactivity and get_mechanism queries

    EMBL-EBI ChEMBL · ChEMBL 2026
    used by WDR5 — the partner that is not a partner: it binds the half of KMT2A the fusion throws away
87. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB P61964 (WDR5_HUMAN) - subcellular location with evidence codes, fetched 2026-09-20

    UniProt Consortium · UniProtKB 2026
    used by WDR5 and KMT2A are at the centrosome and the midbody - a non-chromatin address for both, with a patient-cell phenotype
88. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB Q9UPS6 (SETD1B_HUMAN) - sequence features

    · UniProt Consortium 2026
    used by WDR5 is partitioned, not shared: NSL and SET1/MLL complexes compete for one pool, so perturbing NSL changes how much WDR5 reaches the wild-type KMT2A complex the fusion depends on
89. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB P30291 (WEE1_HUMAN), Wee1-like protein kinase, 646 aa, primary gene name WEE1

    · UniProt Consortium 2026
    used by WEE1 - the one checkpoint target with a KMT2A::AFF1-specific result, and the paper that also found the escape route
90. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 42570285
    Targeting a CDH1-TK1-dependent DNA Synthesis Pathway Overcomes Chemoresistance in Acute Myeloid Leukemia.

    · PubMed record 2026
    used by WEE1 - the one checkpoint target with a KMT2A::AFF1-specific result, and the paper that also found the escape route
91. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.news
    How Komzifti Is Rewriting The Kura Oncology (KURA) Story For Analysts And Investors

    Simply Wall St / Yahoo Finance · Yahoo Finance 2026
    used by What a menin inhibitor costs: the list price, worked out for an infant
92. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.dataset
    NCBI GEO GSE260742 locus table over UCSC mm10 refGene windows, analyses/q117-gained-fusion-occupancy/locus-table.json

    · NCBI Gene Expression Omnibus 2026
    used by What fills the space: RING1B and BCOR arrive at the fusion's sites under BOTH drugs, but the DOT1L inhibitor puts them everywhere on the fusion's territory while the menin inhibitor puts them only in the quartile where the fusion is most completely evicted - and at Meis1 RING1B rises 16-fold
93. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    ENCODE Portal experiment search for target.label BARD1, EXO1 and DNA2, TF ChIP-seq, released, Homo sapiens - HTTP 404 for all three, 2026-09-22

    ENCODE Project Consortium · ENCODE Portal 2026
    used by What is left of the resection absence after the compute was done: the resting state is now MEASURED and negative in 13 ENCODE datasets, so the whole question collapses onto the DAMAGE state, which is never-measured for all six proteins in every cell type on Earth
94. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
    PubMed E-utilities counted-absence searches for genome-wide DSB-mapping assays at KMT2A, run 2026-09-20; querytranslation inspected for each zero

    Q32-break-machinery · NCBI E-utilities 2026
    used by What maps a DNA break, and the fact that none of the modern instruments has ever been pointed at KMT2A in a blood progenitor
95. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
    Europe PMC RESTful Web Service, citations endpoint for MED/37788669, retrieved 2026-09-22

    Europe PMC Consortium · Europe PMC 2026
    used by What the CTCF-protects paper actually cites: it names Gothe and Atkin in ONE direction-free sentence and declares the direction unresolved, and the two papers that ran the reciprocal experiment are absent from all 81 of its references
96. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
    UniProtKB P49711 (CTCF_HUMAN), Transcriptional repressor CTCF, SUBCELLULAR LOCATION comments and note

    UniProt Consortium · UniProtKB 2026
    used by What the CTCF-protects paper actually cites: it names Gothe and Atkin in ONE direction-free sentence and declares the direction unresolved, and the two papers that ran the reciprocal experiment are absent from all 81 of its references
97. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    Oncofusion KG entries protein-aff1-domains (E10 exon-to-codon map for ENST00000395146) and fusion-kmt2a-aff1 (breakpoints bp-kmt2a-intron-11-aff1-e4, bp-kmt2a-intron-9-10-aff1-e4), plus subtraction-aff1-control and subtraction-synthesis-how-general; all read 2026-09-24

    Oncofusion Knowledge Graph · this project 2026
    used by What the paralogues' disease biology says about AFF1: the AFF family shares one SIAH degron — and the index fusion DISCARDS it, because the whole degron lies in the AFF1 leader that the junction at residue 347 throws away
98. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
    PubMed esearch counts for the Q41 Polycomb beat, run and recorded 2026-09-20

    · NCBI PubMed 2026
    used by What the Polycomb beat searched, what it counted as absent, what it read and rejected, and the two absences it got wrong before hand-back
99. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41656387
    A novel human acute myeloid leukemia cell line SDEY-AML1 with KMT2A: MLLT3, IKZF1: EVX1 fusions exhibits high tumorigenicity in NSG mice.

    Yang C, Zhang W, et al. · Sci Rep 2026
    used by What this beat searched, read and set aside - including one cell line the accession database has not caught up with, and one query that returns a clean zero
100. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 42063817
     Mechanism of AF9 (MLLT3)-Partner Dissociation in Mixed-Lineage Leukemia-Rearranged Leukemia.

     Sharma S, Joshi K, Saha A · JACS Au 2026
     used by What this beat searched, read and set aside - including one cell line the accession database has not caught up with, and one query that returns a clean zero
101. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42020782
     A transgenic zebrafish leukemia model driven by KMT2A::MLLT3 (MLL-AF9).

     Saberi M, Delfi O, et al. · Leukemia 2026
     used by What this beat searched, read and set aside - including one cell line the accession database has not caught up with, and one query that returns a clean zero
102. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42613434
     Modeling KRAS mutations in KMT2A::MLLT3 acute myeloid leukemia promotes leukemic progression and transcriptional rewiring.

     Esparza N, Defrêne J, et al. · Leukemia 2026
     used by What this beat searched, read and set aside - including one cell line the accession database has not caught up with, and one query that returns a clean zero
103. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Europe PMC REST search and annotations API records for EXT_ID:37679565

     Europe PMC Consortium · Europe PMC 2026
     used by When a paper will not say what it was done in, ask its data: resolving an unstated experimental system from GEO
104. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     NCBI E-utilities: elink dbfrom=pubmed&db=gds, and esearch db=gds PMID-field behaviour

     · NCBI E-utilities 2026
     used by When a paper will not say what it was done in, ask its data: resolving an unstated experimental system from GEO
105. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysis
     Normal-tissue exposure of the graph's candidate targets, GTEx v8 across 54 tissues

     · Oncofusion knowledge graph (internal analysis) 2026
     used by Where else in the body each target is expressed, and the two controls that say the method works
106. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     UniProtKB Q06609 (RAD51) subcellular-location comments as recorded in this repository's gene-rad51 entry, fetched live 2026-09-21 by that beat; six location values with nine ECO:0000269 attributions to Nucleus and eight to Chromosome, the majority of them in the damage-induced literature

     · UniProt Consortium / this repository 2026
     used by Where RPA actually is: nucleoplasmic and diffuse until there is single-stranded DNA, then punctate prereplication foci at the G1/S border, damage-induced foci with RAD51, and a PML-body pool - and the subunits differ in how well any of this is measured
107. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 41617461
     mTOR Modulation Affects Galectin-1 Expression in KMT2A-rearranged Acute Lymphoblastic Leukemia Cells.

     Pawlik B, Madzio J, Rydzynska Z, Mazurek M, Grzela DP, Walenciak J, Mlynarski W · Anticancer Res 2026
     used by Which immune-evasion routes are actually documented in KMT2A-rearranged disease, and which are borrowed from AML and assumed - a ranked ledger with the bounded absences that define it
108. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB P55197 (AF10_HUMAN) - subcellular location with evidence codes, fetched 2026-09-20

     UniProt Consortium · UniProtKB 2026
     used by Wild-type AF10 is called nuclear on a construct and found in both fractions in tissue - and that disagreement decides whether CALM-AF10's cytoplasmic life is a gain or an inheritance
109. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis
     Re-testing the absence claims that sit before their correction against PubMed today, with query translations recorded

     · Oncofusion knowledge graph (internal analysis) 2026
     used by Working the queue deferred for four cycles: the 40 are three different things, and one absence claim the graph had already refuted ten entries away
110. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB P19544 - Wilms tumor protein (Homo sapiens), reviewed

     UniProt Consortium · UniProtKB/Swiss-Prot 2026
     used by WT1 - Wilms tumour 1, leukaemia antigen and MRD marker, and the widest-margin promoter in the Q152 AFF1-only core
111. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB Q15007 (FL2D_HUMAN), human WTAP, 396 aa

     · UniProt Consortium 2026
     used by WTAP — an oncogenic m6A writer subunit in AML with ZERO records against MLL or KMT2A over six aliases
112. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 42565971
     Beyond nuclear export: chromatin-bound XPO1/CRM1 as a transcriptional scaffold.

     Oka M · International Journal of Hematology 2026
     used by XPO1 / exportin-1 (CRM1) - the cell's main nuclear export receptor, and a chromatin-bound transcriptional scaffold
113. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB entry O14980 (XPO1_HUMAN), SUBCELLULAR LOCATION comment read with evidence codes

     UniProt Consortium · UniProtKB 2026
     used by XPO1 / exportin-1 (CRM1) - the cell's main nuclear export receptor, and a chromatin-bound transcriptional scaffold
114. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 42231094
     Synergistic Antitumor Activity of HAT Inhibitor A485 and XPO1 Inhibitor KPT8602 in Multiple Myeloma.

     Xu H, Wu W, Jiang Y, et al. · Cancer Med 2026
     used by XPO1 / exportin-1 (CRM1) - the cell's main nuclear export receptor, and a chromatin-bound transcriptional scaffold
115. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     cBioPortal for Cancer Genomics - public API, XPO1 (Entrez 7514) mutation query across leukaemia studies

     cBioPortal for Cancer Genomics · cBioPortal public API 2026
     used by XPO1 mutation in acute leukaemia, counted with denominators and a positive control: 1 of 739 B-ALL, 0 of 584 paediatric AML, 0 of 1,103 adult AML
116. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB P46937 (YAP1_HUMAN), Transcriptional coactivator YAP1, feature table and sequence

     UniProt Consortium · UniProtKB 2026
     used by YAP1 (P46937) - the Hippo pathway's transcriptional co-activator, and a KMT2A fusion partner from a completely different functional class
117. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Ensembl REST API lookup, YAP1 (ENSG00000137693), canonical transcript ENST00000282441 with exon and translation coordinates

     Ensembl (EMBL-EBI) · Ensembl REST 2026
     used by YAP1 (P46937) - the Hippo pathway's transcriptional co-activator, and a KMT2A fusion partner from a completely different functional class
118. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41637525
     Small-molecule inhibition of YTHDC1 as a strategy against acute myeloid leukemia in mouse models

     Zhang H, et al. · Sci Transl Med 2026
     used by YTHDC1 — the nuclear m6A reader in the MLL-METTL3-CTCF axis, with an inhibitor, and no dependency signal in KMT2A-rearranged lines
119. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB Q96MU7 (YTDC1_HUMAN), human YTHDC1, 727 aa

     · UniProt Consortium 2026
     used by YTHDC1 — the nuclear m6A reader in the MLL-METTL3-CTCF axis, with an inhibitor, and no dependency signal in KMT2A-rearranged lines
120. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB Q9Y5A9 (YTHD2_HUMAN), human YTHDF2, 579 aa

     · UniProt Consortium 2026
     used by YTHDF2 — the cytoplasmic m6A reader that selectively compromises AML cancer stem cells, discordant across the lineage split here
121. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     UniProtKB - P61981 (1433G_HUMAN), 14-3-3 protein gamma

     · UniProt Knowledgebase 2026
     used by YWHAG / 14-3-3 gamma (P61981) - the only cross-laboratory reproduced KMT2A proximity partner in the curated record, and UniProt places it nowhere near the nucleus
122. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     NCBI PubMed esearch, title-checked bounded queries with querytranslation recorded

     · NCBI E-utilities 2026
     used by YWHAG / 14-3-3 gamma (P61981) - the only cross-laboratory reproduced KMT2A proximity partner in the curated record, and UniProt places it nowhere near the nucleus
123. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     UniProt REST, gene_exact queries for all seven human 14-3-3 paralogues, reviewed records only

     · UniProt Knowledgebase 2026
     used by YWHAG / 14-3-3 gamma (P61981) - the only cross-laboratory reproduced KMT2A proximity partner in the curated record, and UniProt places it nowhere near the nucleus
124. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     IntAct molecular interaction database (EMBL-EBI), PSICQUIC tab27 record for id:P25490 AND id:Q03164

     2026
     used by YY1 - the enhancer-promoter looping factor that recovers KMT2A in a 109-transcription-factor BioID screen
125. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB P25490 (TYY1_HUMAN)

     2026
     used by YY1 - the enhancer-promoter looping factor that recovers KMT2A in a 109-transcription-factor BioID screen
126. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB Q5T200 (ZC3HD_HUMAN), human ZC3H13, 1668 aa

     · UniProt Consortium 2026
     used by ZC3H13 — the m6A writer subunit with the most evenly KMT2A-selective dependency signal in the panel, and almost no literature
127. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     IntAct molecular interaction database (EMBL-EBI), PSICQUIC MITAB 2.7, pubid:39251607, retrieved 2026-09-23

     2026
     used by ZC3H8 / Fliz1 - the last little-elongation-complex subunit without an entry, discovered in fetal liver haematopoietic progenitors, and a selective BioID2 bait that reaches KMT2A in K562
128. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB Q8N5P1 (ZC3H8_HUMAN)

     2026
     used by ZC3H8 / Fliz1 - the last little-elongation-complex subunit without an entry, discovered in fetal liver haematopoietic progenitors, and a selective BioID2 bait that reaches KMT2A in K562
129. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     NCBI PubMed esearch via scripts/pubmed_safe.py, run 2026-09-23; querytranslations recorded: ("ZC3H8"[Title/Abstract] OR "Fliz1"[Title/Abstract]) AND "KMT2A"[Title/Abstract] and the same with "MLL"[Title/Abstract]

     2026
     used by ZC3H8 / Fliz1 - the last little-elongation-complex subunit without an entry, discovered in fetal liver haematopoietic progenitors, and a selective BioID2 bait that reaches KMT2A in K562
130. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
     Human Protein Atlas v25.1, proteinatlas.json.gz record for ZC3H8 (ENSG00000144161), retrieved 2026-09-23

     2026
     used by ZC3H8 / Fliz1 - the last little-elongation-complex subunit without an entry, discovered in fetal liver haematopoietic progenitors, and a selective BioID2 bait that reaches KMT2A in K562
131. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.dataset
     protein-little-elongation-complex (this graph), data.subunits

     2026
     used by ZC3H8 / Fliz1 - the last little-elongation-complex subunit without an entry, discovered in fetal liver haematopoietic progenitors, and a selective BioID2 bait that reaches KMT2A in K562
132. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
     Human Protein Atlas v25.1, subcellular (immunofluorescence) and Blood Atlas records for ZEB2, fetched 2026-09-21

     · Human Protein Atlas 2026
     used by ZEB2 — an EMT transcription factor that turns out to be a leukemia dependency and a guardian of lineage fidelity
133. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 42306066
     CEBP and ZEB2 alterations define three distinct subtypes of B-cell acute lymphoblastic leukemia.

     · Hemasphere 2026
     used by ZEB2 — an EMT transcription factor that turns out to be a leukemia dependency and a guardian of lineage fidelity
134. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     IntAct molecular interaction database, PSICQUIC MITAB 2.7, detection-method and host-organism fields for all nine partner-bait pairs, retrieved 2026-09-21

     · IntAct (EMBL-EBI) 2026
     used by Zero of eight unwritten AFF4/MEN1 partners has an experimentally coded nuclear localisation, and the two that are called nuclear are called it by inference
135. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     RCSB PDB entries 1X5W and 2DMD for UniProt Q9NTW7, and AlphaFold Protein Structure Database entry AF-Q9NTW7-F1, all resolved directly by API

     RCSB Protein Data Bank; AlphaFold Protein Structure Database · Databases 2026
     used by ZFP64 — rank 4 on selectivity, and there is not even a ChEMBL entry for it
136. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 42738274
     Menin Inhibitors in Acute Myeloid Leukemia: Clinical Integration, Resistance, and the Path Beyond Monotherapy

     Zhang TY, Patel SA, Badar T · Cancers (Basel) 2026
     used by Ziftomenib (KO-539, Komzifti) — once-daily menin inhibitor approved in NPM1-mutant AML
137. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     UniProtKB Q15326 (ZMY11_HUMAN), Zinc finger MYND domain-containing protein 11

     UniProt Consortium · UniProt 2026
     used by ZMYND11 (BS69) - an H3.3K36me3 reader that restrains elongation, is itself the 5' partner of a chromatin-hijacking AML fusion driving HOXA/MEIS1/MYB, and whose promoter is the third-strongest MLL1-N bin in RS4;11, ZMYND11::MBTD1 AML is menin-inhibitor sensitive despite having no KMT2A rearrangement, because the translocation deletes ZMYND11's MYND domain and with it a physical brake on wild-type KMT2A, ZMYND11::MBTD1 is the KMT2A-fusion architecture assembled from different parts - and the part it throws away is a direct physical brake on KMT2A itself
138. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     HGNC record HGNC:16966 (ZMYND11) and Ensembl gene ENSG00000015171 on GRCh37 and GRCh38

     HUGO Gene Nomenclature Committee; Ensembl · genenames.org / Ensembl 2026
     used by ZMYND11 (BS69) - an H3.3K36me3 reader that restrains elongation, is itself the 5' partner of a chromatin-hijacking AML fusion driving HOXA/MEIS1/MYB, and whose promoter is the third-strongest MLL1-N bin in RS4;11
139. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     Ensembl GRCh37 REST: lookup/id/ENSG00000015171?expand=1, per-transcript start coordinates

     Ensembl · Ensembl GRCh37 archive 2026
     used by ZMYND11 (BS69) - an H3.3K36me3 reader that restrains elongation, is itself the 5' partner of a chromatin-hijacking AML fusion driving HOXA/MEIS1/MYB, and whose promoter is the third-strongest MLL1-N bin in RS4;11
140. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41454826
     ZMYND11::MBTD1 Fusion in Myeloid/NK Cell Precursor Leukemia: A Case Report With Literature Review and Diagnostic Implications

     Liang H, Su X, et al. · Pediatric Blood & Cancer 2026
     used by ZMYND11::MBTD1, t(10;17)(p15;q21) - a chromatin reader welded to the NuA4/TIP60 acetyltransferase, maintaining Hoxa/Meis1/Myb/Myc/Sox4 in AML: the KMT2A-fusion architecture built from different parts
141. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     NCBI E-utilities esearch db=pubmed via scripts/pubmed_safe.py, 2026-09-23. querytranslation for the first: "ZMYND11"[Title/Abstract] AND "MBTD1"[Title/Abstract]; for the second: "t 10 17"[Title/Abstract] AND "leukemia"[Title/Abstract] (the cytogenetic term was quoted, per the rule that an unquoted t(n;n) inside a group makes PubMed invent a UID filter)

     · NCBI PubMed 2026
     used by ZMYND11::MBTD1, t(10;17)(p15;q21) - a chromatin reader welded to the NuA4/TIP60 acetyltransferase, maintaining Hoxa/Meis1/Myb/Myc/Sox4 in AML: the KMT2A-fusion architecture built from different parts
142. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     NCBI Gene record 401014 (TEX41, Homo sapiens), retrieved live 2026-09-24 by q173 via E-utilities esummary; located by esearch on TEX41[sym] AND human[orgn], which returned exactly one Gene ID

     · NCBI Gene 2026
     used by ZNF384::TEX41 - the case that breaks the family's architecture: ZNF384 is the 5' partner, the 3' partner is a lncRNA, and the fusion is out of frame
143. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
     PubMed E-utilities esearch, 2026-09-21. alias-aware over ZRANB2 and the retired symbol ZNF265, which is where the only localisation paper lives

     · NCBI PubMed 2026
     used by ZRANB2 - the only bait in any published proximity experiment that reaches AFF1, AFF4, ELL, MLLT1, CCNT1, KMT2A and DOT1L at once
144. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40186025
     Heritable maintenance of chromatin modifications confers transcriptional memory of interferon-gamma signaling.

     Mikulski P, Tehrani SSH, Kogan A, Abdul-Zani I, Shell E, James L, et al. · Nat Struct Mol Biol 2025
     used by 'Transcriptional memory' means two different things in this literature, and both of them are used about MLL leukaemia, Prime, wash, divide, rechallenge - the one experiment that would turn 'DOT1L provides transcriptional memory' into a measurement, and it doubles as a dosing-schedule study
145. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39641785
     YAP1::KMT2A-rearranged sarcomas harbor a unique methylation profile and are distinct from sclerosing epithelioid fibrosarcoma and low-grade fibromyxoid sarcoma.

     Warmke LM, Ameline B, Fritchie KJ, et al. · Virchows Arch 2025
     used by 0.2% of profiled sarcomas, median age 38, and every number here has a denominator that is not the population, KMT2A-rearranged soft tissue sarcoma - the same gene as infant B-ALL, in a young adult's leg, as a solid tumour, The menin interface is a requirement of 5'-KMT2A fusions in haematopoiesis, not of KMT2A rearrangement as such - and a solid tumour has been quietly proving it for six years, YAP1::KMT2A::YAP1 (YKY) - an insertional KMT2A rearrangement that keeps the CXXC zinc finger and throws the menin-binding exon away
146. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41139514
     Effect of developmental changes on pharmacokinetics of drugs used in the treatment of infant acute lymphoblastic leukaemia-A comprehensive review.

     de Kluis T, Brigitha LJ, Hanff LM, Huitema ADR, van der Sluis IM, Diekstra MHM · Br J Clin Pharmacol 2025
     used by 6-Mercaptopurine - two years of a nightly tablet whose lethal dose is a genotype, given as a liquid to a baby who cannot swallow it and must not have it with milk, Methotrexate - 5 g/m2 through kidneys that are still maturing, and the one backbone drug the canonical infant sensitivity study never tested, Prednisone - the prophase drug, the prognostic factor, and a prodrug that has never itself been tested on a KMT2A-rearranged blast
147. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 40193715
     Project EVOLVE: an international analysis of postimmunotherapy lineage switch, an emergent form of resistance

     Project EVOLVE consortium · Blood 2025
     used by A CD19 CAR that secretes a CLEC12A bridge: aimed squarely at lineage switch, and it inherits both antigens' failure modes, CD19 - the molecule this disease is treated by, named in 114 entries and written in none of them until now, CD38 - the one marker that is BRIGHTER in KMT2A-rearranged B-ALL, an antigen-targeted therapy that has already produced lineage switch, and an enzyme rather than a receptor, CD7 - the T/NK antigen on a B blast that flags KMT2A rearrangement and worse event-free survival, and the fourth antigen on the lineage-switch list, Competitive release and adaptive therapy — what ecology says happens when you remove the dominant species, Experiment: apply all three pressures and ask whether the survivors are the same cell, Experiment: go back to the diagnostic sample and look for the myeloid clone before it existed, Hypothesis: a single dormant leukemia stem cell state confers cross-resistance to menin inhibition, venetoclax and T-cell engagement at once — the common-cause failure that orthogonal combination therapy assumes away, Hypothesis: KMT2A-rearranged infant ALL is two populations, not one — a mixture-cure model will fit better than proportional hazards, and combination therapy only needs to be given during the first year, Hypothesis: the myeloid clone that appears after CD19-directed therapy was already there at diagnosis, and its abundance is a pre-treatment biomarker, Hypothesis: where a blast goes when the fusion program is released is written in its methylome at diagnosis, not in its transcriptome, Lineage drift - the partial state between B-ALL and AML, and the fact that nobody has published the ORDER in which markers change, Lineage switch as antigen escape from CD19-directed therapy in KMT2A-rearranged leukemia, Lineage switch in KMT2A-rearranged leukemia — the same clone changes what kind of blood cell it is, Mixed-phenotype acute leukemia and KMT2A rearrangement — plasticity caught in the act, Term structure of risk — a steeply falling hazard curve is a statement about heterogeneity, not about time, Where KMT2A-rearranged leukemia physically sits — marrow niche, CNS, blood, liver/spleen and skin, Which marker moves first? A re-analysis of flow files that already exist, to put an order on lineage switch
148. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     KOMZIFTI (ziftomenib) capsules, for oral use - US Prescribing Information (SPL version 1, published 16 Dec 2025)

     Kura Oncology, Inc. · DailyMed / FDA Structured Product Label, setid b650f696-3391-4274-8b55-a5f5e9d04769 2025
     used by A drug that fixes diabetes in mice, and neither label contains the word glucose, Menin builds bone early and blocks it late: two opposite jobs in the same lineage, Menin is required in neural crest for the palate to close - and both menin inhibitors cause cleft palate in animals, Three extra tubes: the glucose study that answers the inversion in children, Twelve weeks of a menin inhibitor in diabetic mice: more beta cells, lower fasting glucose, and nobody looked for a tumour, What the labels measure in a treated child: bone growth, in one sentence, and nothing else endocrine
149. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40399488
     Identification of non-charged 7.44 analogs interacting with the NHR2 domain of RUNX1-ETO with improved antiproliferative effect in RUNX-ETO positive cells.

     Gopalswamy M, Bickel D, Dienstbier N, Tu JW, Vogt M, Schott-Verdugo S, Bhatia S, Etzkorn M, Gohlke H · Sci Rep 2025
     used by A genuine small-molecule disruptor of an oncogenic oligomer DOES exist - 7.44 against the RUNX1::RUNX1T1 NHR2 tetramer - which corrects this graph's record; and its eighteen-year potency curve says the class is a chemistry problem, which is what this graph concluded for the wrong reason
150. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.reviewPMID 40152985
     Menin: from molecular insights to clinical impact.

     Brown MR, Soto-Feliciano YM · Epigenomics 2025
     used by Absence: the tissue with the clinical signal is the one tissue nobody has put under a menin inhibitor and measured - one record in the whole literature, and it is a review
151. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40884014
     A characteristic gene expression profile regulated by ACIN1::NUTM1 fusion in a newly identified infant leukaemic cell line and an ACIN1::NUTM1-inducible model

     Tamai M, Komatsu C, Kagami K, et al. · British Journal of Haematology 2025
     used by ACIN1::NUTM1 - the commonest NUTM1 fusion in infants, cryptic to cytogenetics, and the only one with a human cell line, NUTM1-rearranged B-ALL - the KMT2A-wild-type arm of the same infant trials, with 4-year EFS of 100% against 36-37% next door
152. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 41027490
     Upfront menin-inhibitor resistance in multiply pretreated leukemias

     See PubMed record PMID 41027490 for the full author list (not transcribed here) · Experimental Hematology 2025
     used by Adaptive, non-genetic resistance — the leukemia keeps the fusion and rewires how it is maintained, Analysis (runnable): build the first correlation matrix of menin-inhibitor resistance routes, from screens and from patient cohorts, Analysis (runnable): is there a shared cell-state signature behind non-genetic menin-inhibitor and BET-inhibitor resistance?, Buying an already-impaired asset — what diligence would you do, and what is the biological equivalent?, Duration and reinvestment risk — a 4.6-month response is a short-duration instrument, and short duration changes everything about how you value it, Experiment: does chemotherapy itself install menin-inhibitor resistance? The two-arm controlled test, plus the serial-sample ladder, Hypothesis: genetic and non-genetic escape from menin inhibition are substitutes, so MEN1 mutations will be rare in infants and the field's resistance biomarker will fail in children, Hypothesis: prior therapy itself installs menin-inhibitor resistance, and the dose of prior therapy predicts it better than any mutation does, Hypothesis: reserving menin inhibitors for relapse in infants is actively harmful, because pretreated disease is already resistant, Hypothesis: the ceiling on menin-interface disruption is cell-state plasticity, not target mutation, KMT2D (MLL2/MLL4) - the gene named in this graph's menin-resistance entry, written here for the first time, No second driver means no second target - the quiet genome forecloses the combination logic that works in every other leukaemia, Portfolio theory — a hedge only works against uncorrelated risk, and nobody has estimated the correlation matrix of resistance routes, Reversibility and kinetics — does the program collapse when the fusion is removed, and how fast?, Signalling co-mutations (RAS pathway, FLT3-ITD, WT1) under menin-inhibitor pressure, Systematic enumeration of menin-inhibitor resistance mechanisms: seven entries written, thirteen candidates rejected with reasons, The MLL3/4-UTX switch fails to throw — menin inhibition kills by turning something ON, and cells that cannot turn it on survive, TP53 - named in 84 entries of this graph, absent from the index genome study of the disease, and four different things depending on when you look, TP53 inactivation and the apoptotic threshold — the drug still switches the program off, and the cell still does not die, Track the sub-1% cooperating-lesion clones through menin inhibition, because nobody has measured what the drug selects for, Which step is rate-limiting, and what compensates when you block it — the bite-back map for the causal chain
153. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40536420
     Catalytic Inhibition of KAT6/KAT7 Enhances the Efficacy and Overcomes Primary and Acquired Resistance to Menin Inhibitors in MLL Leukemia.

     · Cancer Discovery 2025
     used by Adaptive, non-genetic resistance — the leukemia keeps the fusion and rewires how it is maintained, ENL stays after the fusion leaves — an epigenetic lesion that outlives the protein that made it, Hypothesis: only a mechanistically orthogonal partner pre-empts menin-inhibitor resistance; a second chromatin agent will not, Testing this corpus's own recorded refusals instead of its gap list overturned the first refusal tried, and the refusal had named the falsifier itself, Which step is rate-limiting, and what compensates when you block it — the bite-back map for the causal chain
154. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 40205054
     Multimodal cell maps as a foundation for structural and functional genomics.

     Schaffer LV, Hu M, Qian G, Moon KM, Pal A, Soni N, Latham AP, Pontano Vaites L, et al. (34 authors), Ideker T · Nature 2025
     used by AFF4-BTK - DECLINED. One osteosarcoma AP-MS row, and it is the only partner in the uncovered prey-only tail with an approved drug against it, which is exactly why the decline is written down, All nine unwritten MEN1 partners trace to exactly two publications, neither of which mentions menin outside an antibody catalogue row, IntAct curates 47 interactions against engineered MLL fusion proteins, and every accession-keyed query in this project is blind to all of them - while its PSICQUIC mirror stops at 2024, MEN1-CD226 is two proteome-scale AP-MS maps, both spoke-expanded, both in cell lines that do not express CD226 - declined, PIP4K2A - the lipid kinase at a genome-wide childhood-ALL susceptibility locus, whose product is the ligand a PHD finger reads
155. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40858576
     Multi-omics analysis identifies an M-MDSC-like immunosuppressive phenotype in lineage-switched AML with KMT2A rearrangement.

     Mikami T, Kato I, Nishimura A, Eguchi-Ishimae M, Kamitori T, Tasaka K, et al. · Nat Commun 2025
     used by After lineage switch, KMT2A-rearranged AML does not merely lose CD19 - it acquires a monocytic myeloid-derived suppressor cell phenotype and actively suppresses T cells, Lineage switch in KMT2A-rearranged leukemia — the same clone changes what kind of blood cell it is, Which immune-evasion routes are actually documented in KMT2A-rearranged disease, and which are borrowed from AML and assumed - a ranked ledger with the bounded absences that define it
156. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus cell line ALL-PO (CVCL_1069)

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by ALL-PO (CVCL_1069) — an infant KMT2A::AFF1 line that is already in DepMap and has never been screened
157. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40724839
     CSPG4.CAR-T Cells Modulate Extracellular Matrix Remodeling in DMD Cardiomyopathy.

     · Int J Mol Sci 2025
     used by An NG2-directed therapy meets pericytes - and unlike B-cell aplasia there is no replacement therapy for a damaged vascular wall, NG2/CSPG4 is the one antigen in the whole surfaceome that KMT2A::AFF1 itself drives - and it is a pericyte and vascular protein, at 124.5 nTPM in normal blood vessel and 246 TPM in tibial artery
158. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40334081
     Clec12a is required for the pathogenesis of NUP98::NSD1 AML.

     Mohanty S, Charles Cano F, Gabdoulline R, Lai CK, Othman B, Sudarsanam H, et al. · Blood Adv 2025
     used by Analysis (planned): is CLEC12A a selective dependency in KMT2A-rearranged lines in DepMap, lineage-split and reported as raw effect?, Clec12a is REQUIRED for NUP98::NSD1 AML pathogenesis - a marker turning out to be a dependency, in a different fusion family, and untested in KMT2A-r, Experiment: CRISPR knockout of CLEC12A in KMT2A-rearranged models, with and without a cooperating RAS lesion, Hypothesis: CLEC12A is a cell-intrinsic dependency in KMT2A-rearranged leukaemia, not only a surface marker - and if so, antigen-negative escape is self-defeating
159. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 41347983
     The promise of menin inhibitors: from approval to triplet regimens

     Thakur RK, Wang ES · Hematology, American Society of Hematology Education Program 2025
     used by Analysis (runnable): can a menin ligand tell KMT2A from JUND? A structural and co-folding selectivity profile of the whole inhibitor class, Experiment: measure the two missing time constants — how fast the KMT2A::AFF1 program collapses on drug, and how fast it comes back off drug, Fiduciary conflict of interest — law does not remove a conflicted agent, it separates the mandates, Hypothesis: adaptive scheduling of menin inhibitors will fail, because MEN1 resistance mutations probably cost the cell nothing, Hypothesis: genetic and non-genetic escape from menin inhibition are substitutes, so MEN1 mutations will be rare in infants and the field's resistance biomarker will fail in children, Hypothesis: menin inhibitors differ in how much JUND they liberate, and the least JUND-liberating compound will be the most durable, Hypothesis: menin-inhibitor effect is hysteretic — the program collapses faster than it recovers — so intermittent dosing can hold efficacy at much lower cumulative exposure, Portfolio theory — a hedge only works against uncorrelated risk, and nobody has estimated the correlation matrix of resistance routes
160. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 40997296
     Ziftomenib in Relapsed or Refractory NPM1-Mutated AML

     Wang ES, Issa GC, Erba HP, et al. · Journal of Clinical Oncology 2025
     used by Analysis (runnable): value a menin inhibitor as a short-duration instrument — cohort meta-regression plus a discrete-event model of remission months, Bounded absence: no menin-inhibitor trial reports response rate by 3-prime fusion partner in the primary literature, Duration and reinvestment risk — a 4.6-month response is a short-duration instrument, and short duration changes everything about how you value it, Eytan Stein (MSKCC), Ghayas Issa (MD Anderson) and the clinical menin-inhibitor investigator network, Hypothesis: the survival benefit of menin inhibition is governed by the rate at which it delivers patients to a curative consolidation, not by its remission rate — and the field is measuring the wrong thing, Kura Oncology — ziftomenib (KO-539): an adults-only sponsor that quietly supplies infant trials, Model: predicting who responds to a menin inhibitor - no patient-level data is public, so this cannot be trained either, Open ground: the questions in this graph that nobody in the landscape appears to be working on, Who holds the data and samples we cannot generate ourselves — an access map
161. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.preprintPMID 38798454
     EZH2-driven immune evasion at disease presentation defines a targetable high-risk subset of acute leukemia exemplified by t(16;21) FUS::ERG AML.

     Buteyn NJ, LaMantia SJ, Burke CG, Sartori VJ, Deering-Gardner E, DeBruine ZJ, et al. · bioRxiv 2025
     used by Another fusion family did the experiment this beat wants: in FUS::ERG and CBFA2T3::GLIS2 AML, MHC class I and II are absent at diagnosis, EZH2 drives it, and an EZH2 inhibitor restores presentation
162. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39749706
     A strong internal promoter drives massive expression of YEATS-domain devoid MLLT3 transcripts in HSC and most lethal AML.

     Bessière C, Zamani A, Pfeifer R, et al. · Cancer Commun (Lond) 2025
     used by Anti-AF9 antibodies see three proteins, not two - and the third is an internal-promoter isoform discovered in 2025
163. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40991369
     Androgen receptor signaling as a new target for intervention in acute myeloid leukemia.

     · Blood Adv 2025
     used by AR / androgen receptor - the best-supported partner in the absence set by independent-publication count, and the reason a menin inhibitor is in prostate cancer trials
164. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40935826
     Acute myeloid leukaemia cells express high levels of androgen receptor but do not depend on androgen signaling for survival.

     · Leukemia 2025
     used by AR / androgen receptor - the best-supported partner in the absence set by independent-publication count, and the reason a menin inhibitor is in prostate cancer trials
165. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 40440427
     ASB7 is a negative regulator of H3K9me3 homeostasis.

     Zhou J, Chen Y, et al. · Science 2025
     used by ASB7 (Q9H672) - the brake on H3K9me3's own positive feedback loop, released by CDK1 in mitosis, and it reached this graph as the flattest dependency in the read queue, No H3K9me3 writer and no H3K9me3 reader has ever been localised at the KMT2A locus IN THE PUBLISHED LITERATURE, in any cell type: 20 queries, 5 alias spellings, 0 on-topic records - and CORRECTED 2026-09-22: the SUV39H1 half is no longer unanswerable from archives. ENCODE still holds zero SUV39H1 experiments (verified by three routes with controls), but GEO holds two deposits, and Q114 read both at this locus and found the writer ABSENT
166. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.preprintPMID 40672274
     Selective Sensitivity of Ph-like B-ALL to BRG1 Inhibition Reveals a Novel Targeted Therapy Strategy.

     Abhinav Ayyadevara VSS, Gaur S, Paik A, Perencsik R, et al. · bioRxiv 2025
     used by BAF inhibition against the menin axis: on the evidence it is a complement, not an alternative - and the case rests on one laboratory, FHD-286 - the dual BRG1/BRM inhibitor that carries every SWI/SNF therapeutic claim in this disease, with a minimum enrolment age of 16, SMARCA2 (BRM) - the paralogue nobody measured, and the reason a DepMap rank cannot predict what a BRG1/BRM inhibitor does, SMARCA4 (BRG1) - a tumour suppressor by mutation and a maintenance requirement by knockdown, and in KMT2A-rearranged lines the dependency data say it is not selective at all, The SWI/SNF dependency in KMT2A-rearranged leukaemia belongs to ncBAF, not to canonical BAF - and the drug in the clinic is aimed at the wrong module
167. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40592879
     BAHCC1 binds H4K20me1 to facilitate the MCM complex loading and DNA replication

     Li D, Zhang ZM, Mei L, Yu Y, Guo Y, Mackintosh SG, et al. · Nat Commun 2025
     used by BAHCC1 - a BAH-domain H3K27me3 reader that an MLL fusion binds and upregulates in mouse, and the locus carrying the two largest MLL1-N-reactive rises under a menin inhibitor in human RS4;11, H4K20me1 - the transcription- and replication-linked H4 state, whose gene-body level tracks Pol II; it HAS been profiled genome-wide in human haematopoietic stem cells twice, and a query scoped to 'leukemia' cannot see either dataset
168. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40682820
     BAHCC1 promotes gene expression in neuronal cells by antagonizing SIN3A-HDAC1

     Monziani A, Perry RB, Hezroni H, Ulitsky I · Nucleic Acids Res 2025
     used by BAHCC1 - a BAH-domain H3K27me3 reader that an MLL fusion binds and upregulates in mouse, and the locus carrying the two largest MLL1-N-reactive rises under a menin inhibitor in human RS4;11
169. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 40710017
     Therapeutic Implications of Menin Inhibitors in the Treatment of Acute Leukemia: A Critical Review

     Canichella M, Papayannidis C, Mazzone C, de Fabritiis P · Diseases 2025
     used by Biomea Fusion — icovamenib (BMF-219): the covalent menin inhibitor that left oncology for diabetes, Bleximenib (JNJ-75276617) — menin inhibitor with a cleaner cardiac profile, and the only one with a 2-year-old floor, Enzomenib (DSP-5336) — menin inhibitor with the highest reported KMT2A-r response rate and little differentiation syndrome, Johnson & Johnson / Janssen — bleximenib (JNJ-75276617): paediatric from age 2, but not infants, and the dedicated child study was withdrawn, Sumitomo Pharma — enzomenib (DSP-5336): one trial, adolescents at 12 years and 40 kg, no paediatric programme
170. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     ChEMBL compound record: BLEXIMENIB (CHEMBL5314509)

     EMBL-EBI ChEMBL Database · ChEMBL 2025
     used by Bleximenib (JNJ-75276617) — menin inhibitor with a cleaner cardiac profile, and the only one with a 2-year-old floor
171. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.preprint
     Bleximenib in combination with intensive chemotherapy: A phase 1b study in newly diagnosed Acute Myeloid Leukemia with KMT2A or NPM1 alterations

     Johnson & Johnson / cAMeLot investigators · Blood 146 (Supplement 1), ASH Annual Meeting abstract 2025
     used by Bleximenib (JNJ-75276617) — menin inhibitor with a cleaner cardiac profile, and the only one with a 2-year-old floor
172. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.preprint
     Phase 1b study of bleximenib in combination with venetoclax in Acute Myeloid Leukemia with KMT2A or NPM1 alterations

     Johnson & Johnson / cAMeLot investigators · Blood 146 (Supplement 1), ASH Annual Meeting abstract 5200 2025
     used by Bleximenib (JNJ-75276617) — menin inhibitor with a cleaner cardiac profile, and the only one with a 2-year-old floor
173. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus cell line BLIN-3 (CVCL_QW47)

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by BLIN-3 (CVCL_QW47) — a three-month-old's KMT2A::AFF1 line used to show the pro-B to pre-B block can be pushed
174. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.preprint
     Boltz-2: Towards Accurate and Efficient Binding Affinity Prediction

     Passaro S, Corso G, Wohlwend J, et al. · bioRxiv 2025
     used by Boltz co-folding plan: six complexes worth folding, three that must not be, and the positive controls that decide whether to believe any of it, Compute: which backend for which piece of phase-2 work, and the one constraint that matters for each, Phase-2 dossier: the non-small-molecule modalities - degraders first, and the honest limits of each
175. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     REVUFORJ (revumenib) tablets, for oral use - US full prescribing information (NDA 218944)

     Syndax Pharmaceuticals / US FDA · DailyMed / Drugs@FDA (NDA 218944) 2025
     used by Both approved menin inhibitors cause multi-organ hyperplasia in animals, and one of them in the pancreas irreversibly, FDA already required this study: PMR 4730-1 names endocrine-related disorders due to chronic menin inhibition, How long does menin have to be gone? Two months in a mouse islet, a decade or more in a human carrier, Hypothesis: the PTH rise on menin inhibitors is on-target and exposure-dependent, not renal, Intact PTH rises in 34% of patients on revumenib, and hyperparathyroidism is on the label, Irreversible femoral growth-plate closure in juvenile rats: the label already tells paediatricians to watch growth, Pancreatic neuroendocrine tumours in MEN1: the manifestation that kills, and the one the animal data points at, Pituitary adenoma in MEN1: the third manifestation, and the one that matters most for a growing child, Primary hyperparathyroidism in MEN1: the first and commonest consequence of losing menin, Reading the same-source counter-evidence: 77 notes adjudicated, and the defect is not the one the metric measures, Revumenib (SNDX-5613, Revuforj) — first approved menin–KMT2A interface inhibitor, The cheapest study that would settle this: nine assays and a hand radiograph, on children already being followed, The reversibility question: months of partial occupancy against a syndrome built from decades of loss, The same pocket suppresses JUND: menin inhibition's unmeasured endocrine liability in infants, The whole bone-mineral axis moves on revumenib: phosphate in 51%, alkaline phosphatase in 33%, calcium in 15%
176. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     KOMZIFTI (ziftomenib) capsules, for oral use - US full prescribing information

     Kura Oncology / US FDA · DailyMed / Drugs@FDA 2025
     used by Both approved menin inhibitors cause multi-organ hyperplasia in animals, and one of them in the pancreas irreversibly, The whole bone-mineral axis moves on revumenib: phosphate in 51%, alkaline phosphatase in 33%, calcium in 15%
177. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40000924
     Genetic Diversity in KMT2A-r and KMT2A-Wt Groups: Assessing the Prognostic Value of Markers in BCP-ALL Among Infants

     Ilyasova K, Zerkalenkova E, Soldatkina O, et al. · International Journal of Laboratory Hematology 2025
     used by BRD9::NUTM1, t(5;15)(p15.33;q14) - one fusion is enough to make infant B-ALL in a mouse, and it is the one that behaves best in a child, Infant BCP-ALL (n=175): KMT2A::AFF1 2-year EFS 36% versus 37% for every other partner (P=0.9), JPLSG MLL-10 (n=90 infants): a 38-point EFS split built from age, CNS status and MRD, with the partner never entering the model, NUTM1-rearranged B-ALL - the KMT2A-wild-type arm of the same infant trials, with 4-year EFS of 100% against 36-37% next door, The clinical outcome data do not support a single KMT2A class, and they do not refute the menin interface either
178. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     FDA approves revumenib for relapsed or refractory acute myeloid leukemia with a susceptible NPM1 mutation

     US Food and Drug Administration, Oncology Center of Excellence · FDA Resources Information Approved Drugs 2025
     used by Breakthrough therapy and accelerated approval: the menin field took the fast review and declined the shortcut, Revumenib (SNDX-5613, Revuforj) — first approved menin–KMT2A interface inhibitor, The rare paediatric disease priority review voucher: a $150-200m bearer bond, lapsed for 14 months, now live to 2029
179. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 40136298
     Factors in Time to Full Approval or Withdrawal for Anticancer Medicines Granted Accelerated Approval by the FDA.

     Tibau A, Hwang TJ, Romano A, Borrell M, Gich I, Molto C, Kesselheim AS · JAMA Network Open 8(3):e252026 2025
     used by Breakthrough therapy and accelerated approval: the menin field took the fast review and declined the shortcut
180. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.news
     FDA Approves Ziftomenib for NPM1-Positive AML

     The ASCO Post · The ASCO Post 2025
     used by Breakthrough therapy and accelerated approval: the menin field took the fast review and declined the shortcut
181. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39938805
     Younger children with nonmalignant disease have increased incidence of mixed myeloid chimerism after allogeneic hematopoietic cell transplantation with busulfan-based conditioning.

     Dvorak CC, Temple WC, Cisneros GS, Chu J, Winestone LE, Higham CS, Shimano KA, Kharbanda S, et al. · Transplantation and Cellular Therapy 2025
     used by Busulfan - the alkylating agent that replaces radiation in infant conditioning, and whose labelled paediatric target range is below the range the modern trial data support, Infants are not small children - four maturing organ systems, three conditioning drugs, and a protocol that treats the first year of life as one category, Mixed donor chimerism under three years of age - the same drug exposure ablates less marrow in a younger child, and dosing cannot fix it
182. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40875517
     CTCF Is Essential for the Development and Maintenance of CALM-AF10-Induced Leukemia.

     Kuroki Y, et al. · Cancer Sci 2025
     used by CALM-AF10 reaches DOT1L through exactly the same OM-LZ interface as KMT2A::MLLT10 - the recruitment transfers, the addressing does not, CTCF keeps CALM-AF10 leukaemia undifferentiated through TGM2 - an architectural dependency, not a menin one
183. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40722046
     HDAC7 induction combined with standard-of-care chemotherapy provides a therapeutic advantage in t(4;11) infant B-cell acute lymphoblastic leukemia.

     de Barrios O, Ocon-Gabarro I, Gusi-Vives M, Collazo O, Meler A, Romecin PA, et al. · Biomarker Research 13(1):99 2025
     used by Catalytic-dead versus degrader: a four-arm test that resolves the HDAC7 direction conflict and supplies the pharmacodynamic marker this drug class has never had, Chidamide (tucidinostat) - the HDAC inhibitor in both of this graph's menin-inhibitor combination papers, and the only one paired with a menin inhibitor in the lymphoid index disease, EZH2 - the Polycomb enzyme that collaborates with the fusion instead of opposing it, and that no single-agent inhibitor can switch off, HDAC7 - the eraser the index fusion silences, where the proposed therapy is to INDUCE the HDAC, and two 2024-2025 papers point in opposite directions, Measure H3K27me3 after a menin inhibitor - the free pharmacodynamic nobody has read, and the one experiment that separates two mechanisms, No HDAC-inhibitor result in this disease attributes to an HDAC enzyme - the only per-enzyme evidence is genetic, and it says the enzyme is not fusion-specific, PRC2 - the complex, not the subunit, is the unit every experiment in this disease actually resolves, PRC2 is the fusion's repressive arm, recruited through menin, and the index disease's version of it runs to HDAC7, RUNX2 - a direct KMT2A-chimera target and dependency in T-ALL, a patient-specific enhancer target in KMT2A::AFF1 B-ALL, and the gene a menin inhibitor represses to restore steroid sensitivity in t(4;11) infants, The HDAC7 direction conflict is scaffold versus catalysis: removing the protein and blocking its catalysis are opposite interventions, because class IIa HDACs barely have any catalysis, Trithorax against Polycomb at HOXA: the textbook antagonism, and the two ways this disease breaks it
184. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39823827
     Exploring treatment-driven subclonal evolution of prognostic triple biomarkers: Dual gene fusions and chimeric RNA variants in novel subtypes of acute myeloid leukemia patients with KMT2A rearrangement.

     Xu Y, Li SC, Xiao J, Liu Q, Cherukuri D, Liu Y, Mirshahidi S, Xu J, Chen X, et al. · Drug Resistance Updates 2025
     used by CBX3 / HP1-gamma (Q13185, 183 aa) - the EUCHROMATIC HP1 paralogue, and the one CTCF actually prefers: the reader that carries BRCA1/BARD1 onto H3K9-methylated break chromatin, flat in DepMap, and a fusion partner in one KMT2A::AFDN AML patient, CCDC32::CBX3, a previously unreported second fusion found alongside KMT2A::AFDN in a relapsing AML - and the only record in PubMed that pairs CBX3 with KMT2A at all
185. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39962076
     CHAMP1 complex directs heterochromatin assembly and promotes homology-directed DNA repair.

     Li F, Zhang T, Syed A, Elbakry A, et al. · Nature Communications 2025
     used by CBX5 / HP1-alpha (P45973, 191 aa) - the H3K9me3 reader that recruits the writer, the writer's destroyer and the second writer; and the one member of that circuit with a published pro-leukaemic role, as part of an MLL leukaemia stem-cell programme that immortalises myeloid progenitors WITHOUT Hoxa or Meis, SETDB1 (Q15047, KMT1E/ESET) - the second H3K9me3 writer: it represses the fusion's own targets via the PAF1 complex, it is required in fetal liver HSPCs and in leukaemic stem cells, and it is a broad dependency in half the CRISPR panel - three published directions that do not agree
186. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 40979068
     Targeting CDK9 inhibits the growth of KMT2A-rearranged infant leukemia and demonstrates synergy with menin inhibition.

     Sharma R, Zhang C, Shah R, Frigault MM, Johnson AJ, Mangum DS, Maese LD, Lacayo NJ, Narendran A · Blood Neoplasia 2025
     used by CDK9 - the kinase the whole SEC story runs through, which this graph held only as half of a two-protein summary entry, CDK9 inhibition in KMT2A-rearranged infant leukemia — the most direct hit on the hijacked machinery, and the narrowest window, Hitting the same axis at two points was predicted to be sub-additive; the one published test found synergy in all four KMT2A-rearranged lines, MYC reactivation through PRC1.1 loss — a named, druggable bypass out of menin dependence, The length-matched control I demanded of myself: 42% of the abstract-to-full-text rise is reproduced by an unrelated same-field paper, so the specificity I claimed for it was roughly half what I reported, What was searched, what came back empty, and what was read and not used - the P-TEFb reservoir beat's audit trail
187. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41339993
     Abnormal nuclear and nucleolar immunoreactivity of p16INK4a represents a frameshift alteration in CDKN2A: the E6H4 clone recognizes the "p14ARF::p16INK4a" chimeric protein.

     Mitsui A, et al. · Virchows Arch 2025 2025
     used by CDKN2A - one gene, two reviewed UniProt records with the same primary symbol, and a deletion that is three times rarer here than in the infant leukaemias next door
188. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.preprintPMID 41279447
     Co-targeting menin and LSD1 dismantles oncogenic programs and restores differentiation in MLL-rearranged AML.

     Tayari MM, Dos Santos HG, Beckedorff F, et al. · bioRxiv 2025
     used by Census of every published chromatin-occupancy measurement made under a menin inhibitor: eight datasets, every one TSS-anchored, every one tabulating losses only, LEDGF occupancy under revumenib: the measurement the graph called missing exists, in one 2025 preprint, and it goes the way the tenfold cooperativity predicts, The clearest clinical rationale for a LEDGF agent - second line after menin-inhibitor failure - has never been tested, and one 2025 measurement now argues against it, Three routes to one observation: the CUT&RUN panel that says whether menin eviction, H3K36me3 loss or MLL loss takes LEDGF off the fusion's genes
189. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.reviewPMID 40207717
     KMT2A-rearranged acute lymphoblastic leukemia in infants: current progress and challenges

     Stutterheim J, van der Sluis IM, Pieters R, et al. · Haematologica 2025
     used by Central nervous system involvement at diagnosis in KMT2A-rearranged infant leukaemia, CNS disease at diagnosis in infants: a real excess, measured by a procedure that partly creates it, Dying in induction: the place where infant protocols actually differ, Infant acute lymphoblastic leukaemia (ALL diagnosed under 1 year of age), MCL1 plus BCL-2 plus dexamethasone: a triple combination that matched induction chemotherapy in infant PDX models, Nine survivors in ten carry a long-term complication, and it is worse the younger they were, The ANZCHOG infant cohort: 119 babies, with the presenting features actually tabulated, Treating the five menin inhibitors as one drug, when a 2026 title says they are not, When infant leukaemia comes back, it comes back early and while treatment is still running, Zoledronic acid against the osteoclast: a bone-marrow-niche target, but not tested in infant KMT2A-rearranged disease
190. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40965326
     Balancing benefit and burden: treatment intensification in paediatric KMT2A rearrangements acute myeloid leukaemia.

     Fayez H, Elsherif M, et al. · Acta Oncol 2025
     used by Children's Cancer Hospital Egypt (n=150 KMT2A-r): EFS 50% to 17% across four partner groups in a single-centre cohort
191. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40204893
     DEK::NUP214 acts as an XPO1-dependent transcriptional activator of essential leukemia genes.

     Kaya F, Bewicke-Copley F, Miettinen JJ, et al. · Leukemia 2025
     used by Chromatin-bound XPO1 as a shared, druggable address for HOXA-driven leukaemia - and the objection that it may be a general chromatin cofactor rather than an address at all, DEK::NUP214 is the sixth lesion on the XPO1 address - and the only one where the drug response was measured in primary patient cells, Docking onto pre-bound XPO1 is a general route to leukaemic chromatin, used by at least seven different lesions - not three coincidences, Eltanexor (KPT-8602) - the second-generation SINE whose whole point is that you can give it more often, FOXC1 - a mesenchymal forkhead factor derepressed in HOXA-high AML that blocks monocytic differentiation, with a real mechanism and zero published connection to KMT2A rearrangement, NUP214 / CAN - the cytoplasmic-face nucleoporin that CRM1 docks against, and the 3' partner of four leukaemia fusions, The reciprocal ChIP: is chromatin-bound XPO1 present in a KMT2A-rearranged cell, and does a menin inhibitor move it?
192. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39704147
     Bleximenib, the novel menin-KMT2A inhibitor JNJ-75276617, impairs long-term proliferation and immune evasion in acute myeloid leukemia.

     Hogeling SM, Le DM, La Rose N, Kwon MC, Wierenga ATJ, Van den Heuvel FAJ, et al., Schuringa JJ · Haematologica 2025
     used by CIITA - the class II transactivator, a gene menin sits on, and the only antigen-presentation gene in this disease with a knockout that proves the drug acts through it, GMP-like state — the destination of therapy-driven lineage switch and, separately, the state most sensitive to menin inhibition, Granulocyte-monocyte progenitor (GMP) — the committed cell an MLL fusion can turn back into a stem cell, HLA-A - the class I heavy chain a menin inhibitor was actually measured on, and the human orthologue of the MHC class I molecule that protects MLL-AF9 leukaemia stem cells from NK cells, Hypothesis: a menin inhibitor must come BEFORE an antigen-directed immunotherapy, not with it or after it - and every published experiment has already assumed this without anyone testing it, Hypothesis: menin inhibition pushes cells toward the GMP-like state, and the GMP-like state is where menin inhibition works best — so a lineage switch on therapy should predict response, not failure, Hypothesis: menin-inhibitor sensitivity falls with cell-cycle exit, so the compartment that causes relapse is the one the drug reaches least — and nobody has sorted by cycle state to check, MHC class I is a bivalent gene set, and a menin inhibitor derepresses it - shown in K-562, SCLC and neuroblastoma, and measured on HLA-A in primary AML, but never once in a KMT2A-rearranged cell, Raising MHC class I is not a free good: the same molecule is the inhibitory ligand that holds NK cells off, and in this fusion family it is an in vivo leukaemia dependency, Systematic enumeration of menin-inhibitor resistance mechanisms: seven entries written, thirteen candidates rejected with reasons, The class I and class II arms of menin inhibition are different mechanisms - the class I effect was tested against viral mimicry and NF-kB and excluded both, The GMP-like state is being used as a therapeutic anchor in two independent arguments, and its chromatin definition rests on one post-lineage-switch sample that also defined it, The monocytic confound is worse than recorded: two of the six rearranged lines are one patient, and the four-line control group contains a HOXA-driven fusion and two NPM1c/myelomonocytic lines
193. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     KOMZIFTI (ziftomenib) US prescribing information, indications and usage

     Kura Oncology · FDA Structured Product Label via openFDA, SPL id 3213879b-dd88-413b-9910-8fd422c99805, effective 2025-12-09 2025
     used by Counted absence: no menin-inhibitor trial has ever reported a response RATE in NUP98-rearranged patients
194. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40080525
     SMYD3 Activates Fatty Acid beta-Oxidation to Promote Self-Renewal of Leukemia Stem Cells.

     Zhou M, Wu Z, Wei F et al · Cancer Research 2025
     used by CPT1A - the outer-mitochondrial-membrane fatty-acid gatekeeper that is also a lysine succinyltransferase, fused to KMT2A exon 3 in the one case that is tether WITHOUT address, SMYD3 - a lysine methyltransferase with three claimed histone marks and one robust non-histone substrate, sitting on an HOXA9 feed-forward loop in MLL-AF9 AML and a fatty-acid-oxidation axis in CML stem cells, with zero interventional trials
195. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40393984
     CREBBP inactivation sensitizes B cell acute lymphoblastic leukemia to ferroptotic cell death upon BCL2 inhibition.

     Garcia-Gimenez A; Ditcham JE; Azazi DMA; Giotopoulos G; Asby R; Meduri E; Bagri J; Sakakini N; Lopez CK; Narayan N; Beinortas T; Agrawal-Singh S; Fung K; O'Connor D; Mansour MR; Alabed HBR; Jenkins B; Koulman A; Murphy MP; Horton SJ; Huntly BJP; Richardson SE · Nat Commun 2025
     used by CREBBP (CBP) — binds the KMT2A transactivation domain, which no fusion keeps
196. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39513582
     Nucleolar casein kinase 2 alpha as a prognostic factor in patients with surgically resected early‑stage lung adenocarcinoma.

     Muto S, Homma MK, Kiko Y, Ozaki Y, Watanabe M, Okabe N, Hamada K, Hashimoto Y, Suzuki H · Oncol Rep 2025
     used by CSNK2A1 (casein kinase 2 alpha) - the one kinase that turns up three separate times in KMT2A biology
197. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40643484
     CK2α Deletion in the Hematopoietic Compartment Shows a Mild Alteration in Terminally Differentiated Cells and the Expansion of Stem Cells.

     Rajaiah R, Daniyal M, Shanmugam MP, Valensi H, Duke K, Mercer K, Klink M, Lanza M, Uzun Y, Huang S, Dovat S, Behura CG · Cells 2025
     used by CSNK2A1 (casein kinase 2 alpha) - the one kinase that turns up three separate times in KMT2A biology
198. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41430607
     The METTL3-YTHDC1 axis mediates architectural RNA m6A modification to modulate the integrity of chromatin TADs in MLLr+ AML genome

     Fu R, Yu W, Zhao R, Yang H, Cao B, Dai C, Qianjiang H, Xia Y, Wang L, Lu J, Zhou R, Shi A, Lou H, Zhang X, Luo H · Molecular Cancer 2025
     used by CTCF/cohesin boundaries and the HOXA topological domain — the 3D scaffold the fusion program runs on, METTL3 — the m6A writer with a clinical-grade inhibitor, an MLL-rearranged AML mechanism, and a B-lymphoid signal that goes the wrong way, RNA m6A (METTL3/YTHDF/YTHDC1) in KMT2A-rearranged leukemia — the empty cell that turned out not to be empty, Transcription–replication conflict as the candidate reason KMT2A-rearranged cells need the Fanconi pathway — a chain with two measured links and three inferred ones, YTHDC1 — the nuclear m6A reader in the MLL-METTL3-CTCF axis, with an inhibitor, and no dependency signal in KMT2A-rearranged lines
199. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41411610
     Minimal Residual Disease Detection in Peripheral Blood of Patients With High-Risk Neuroblastoma Correlates With Outcome in the International GPOH-DCOG Prospective Validation Study.

     Gelineau NU, van Zogchel LMJ, De Carolis B, et al. · JCO Precis Oncol 2025
     used by ctDNA MRD under a menin inhibitor: blood flow diverges from blood DNA, because the disease is in the spleen and marrow
200. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41129592
     Paf1C regulates the Neurospora circadian clock by promoting the transcription elongation of frequency.

     · PLoS Genet 2025
     used by CTR9 — a PAF1C subunit the field assumes is a fusion partner, with no paper that tested it
201. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset
     GEO sample records GSM9032979, GSM9032981, GSM9032985, GSM9032987, chip antibody / antibody vendor / antibody catalog_number fields, fetched individually 2026-09-23

     · NCBI Gene Expression Omnibus 2025
     used by Cycle 102 declared before it ran that an input pair 'bounds library and coverage variation but NOT ChIP efficiency' and is therefore a LOWER BOUND - the size of that underestimate is now measured in human KMT2A::AFF1 MV4;11 and it is sixteen-fold at the peaks: 0.6% for an input pair against 9.4% for a menin ChIP pair over the same bins, in the same cells, on the same day
202. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39754404
     KMT2A degradation is observed in decitabine-responsive acute lymphoblastic leukemia cells.

     Brock L, Benzien L, Lange S, et al. · Mol Oncol 2025
     used by Decitabine - degrades DNMT1, and in ALL cells it degrades KMT2A too: the hypomethylating agent with two mechanisms and a menin-inhibitor combination already in the clinic, Decitabine degrades DNMT1 - and in ALL cells the same treatment lowers KMT2A protein, with the shared CXXC-family DNA-binding module offered as the reason, DNMT1 - the antagonist: its CXXC domain reads unmethylated CpG in order to STOP methylation, and it is the only heterologous CXXC that runs an MLL-AF9 leukaemia
203. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40186895
     Discovery of the first-in-class DOT1L PROTAC degrader.

     Yim H, Sun R, Xu Z, et al. · Eur J Med Chem 2025
     used by Degrade DOT1L, inhibit DOT1L, or leave a dead enzyme in place - run all three against the same cells and the same marrow, DOT1L does things that have nothing to do with methylation - which is why blocking its active site was never going to remove all of it, How much sugar the cell has decides how much DOT1L there is - a metabolic dial on the leukaemia's mark, MS2133 - the first molecule to degrade DOT1L rather than inhibit it
204. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39443736
     NPM1-fusion proteins promote myeloid leukemogenesis through XPO1-dependent HOX activation.

     Shimosato Y, Yamamoto K, Jia Y, et al. · Leukemia 2025
     used by Docking onto pre-bound XPO1 is a general route to leukaemic chromatin, used by at least seven different lesions - not three coincidences
205. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41192422
     Disparate leukemia mutations converge on nuclear phase-separated condensates.

     Datar GK, Khabusheva E, Anand A, et al. · Cell 2025
     used by Docking onto pre-bound XPO1 is a general route to leukaemic chromatin, used by at least seven different lesions - not three coincidences, NPM1 (nucleophosmin) — the nucleolar shuttle whose mutant form binds chromatin with KMT2A and buys the second menin-inhibitor indication, NPM1c and XPO1: one drug, one output, two incompatible mechanisms - is the mutant needed in the cytoplasm or on the chromatin?, NUP98 FG condensates, audited assay by assay: no half-bleach has ever been done and no NUP98 fusion has ever been endogenously tagged, Two pools of one protein: the chromatin-bound XPO1 that matters here has never been separated biochemically from the soluble export machine
206. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 39793445
     A first-in-human phase 1/2 dose-escalation study of MAK683 (EED inhibitor) in patients with advanced malignancies.

     Ribrag V, Iglesias L, De Braud F, Ma B, Yokota T, Zander T, et al. · Eur J Cancer 2025
     used by EED - the PRC2 subunit this disease actually needs, with drugs in the clinic and zero leukaemia studies, H3K27me3 - the repressive mark this graph argued about for seventy-seven cycles without ever writing an entry for it, Measure H3K27me3 after a menin inhibitor - the free pharmacodynamic nobody has read, and the one experiment that separates two mechanisms, Point the EED inhibitor at the index fusion - a clinical-stage drug, a subunit with no paralogue, and zero leukaemia experiments
207. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40780499
     The myeloid transcription factor Elf1 regulates genes with function in innate immunity.

     Varghese P, Garcia-Cuellar MP, Slany RK · Exp Hematol 2025
     used by ELF1 - a direct transcriptional target of MLL fusion proteins and HOXA9 that is ALSO a BioID neighbour of KMT2A, and that is focally deleted in paediatric AML without a KMT2A rearrangement
208. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus records for CVCL_S906, CVCL_S907, CVCL_8866, CVCL_AY52, CVCL_QW62, CVCL_QW67, CVCL_QW66, CVCL_0081 and CVCL_A088

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by Enumeration for the index-fusion model beat: what was searched, found, rejected and could not be read
209. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.preprint
     Monotherapy update from the Phase 1 portion of the Phase 1/2 trial of the menin-MLL inhibitor enzomenib (DSP-5336) in patients with relapsed or refractory acute leukemia

     Horizen-1 investigators / Sumitomo Pharma America · Blood 146 (Supplement 1): 763, ASH Annual Meeting abstract 2025
     used by Enzomenib (DSP-5336) — menin inhibitor with the highest reported KMT2A-r response rate and little differentiation syndrome
210. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.news
     Menin Inhibitor Enzomenib Gains FDA Orphan Drug Designation in ALL

     Targeted Oncology editorial staff · Targeted Oncology 2025
     used by Enzomenib (DSP-5336) — menin inhibitor with the highest reported KMT2A-r response rate and little differentiation syndrome
211. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40858905
     ERG-driven prostate cancer initiation is cell-context dependent and requires KMT2A and DOT1L

     Feng W, Ladewig E, Lange M, Salsabeel N, Zhao H, Lee YS, Gopalan A, Luo H, et al. · Nature Genetics 57:2177-2191 2025
     used by ERG - a heptad stem-cell transcription factor whose 15 mentions in this graph are mostly about OTHER diseases, and whose best-established role in B-ALL is loss of function, not cooperation
212. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40294241
     Single-cell Transcriptional Atlas of Human Hematopoiesis Reveals Genetic and Hierarchy-Based Determinants of Aberrant AML Differentiation.

     Zeng AGX, Iacobucci I, Shah S, Mitchell A, Wong G, Bansal S, et al., Dick JE · Blood Cancer Discov 2025
     used by Erythroid progenitor - the committed red-cell precursor, distinct from the bipotent MEP that two entries had to borrow, and the compartment that pays for any haem-pathway or fetal-globin intervention
213. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.journal-articlePMID 40516531
     Combined inhibition of KAT6A/B and Menin reverses estrogen receptor-driven gene expression programs in breast cancer

     Olsen SN, et al., Armstrong SA · Cell Reports Medicine 2025
     used by ESR1 / estrogen receptor alpha - menin's best-documented non-leukaemic partner, and the only one a menin inhibitor is being given to patients to disrupt on purpose
214. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39656971
     Progressive chromatin rewiring by ETO2::GLIS2 revealed in a genome-edited human iPSC model of pediatric leukemia initiation

     Boudia F, Baille M, Babin L, et al. (senior author Mercher T) · Blood 2025
     used by ETO2::GLIS2 rewires chromatin in stages and hijacks the osteogenic homeobox factor DLX3 as its first required step — a genome-edited human iPSC model that resolves leukaemia initiation into an ordered sequence
215. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39891826
     Establishment of a high-risk pediatric AML-derived cell line YCU-AML2 with genetic and metabolic vulnerabilities.

     Ikeda J, Shiba N, Kato S, et al. · Int J Hematol 2025
     used by Every human t(9;11) cell line, with every accession fetched and read back: eleven lines, ten patients, and two of them are B-ALL
216. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40944346
     LDB1::KMT2A Fusion in a Spindle-Cell Sarcoma: A Case Report.

     Wang Z, Zhang Y, Zhu M, et al. · Genes Chromosomes Cancer 2025
     used by Every published KMT2A partner in sarcoma, counted - plus the papers this beat read and did not use, so the next beat does not repeat the search without the decisions, In leukaemia KMT2A gives the front of the protein; in sarcoma it gives the back. Every consequence follows from that., LDB1 (Q86U70) - and the sarcoma fusion keeps the part that self-associates while losing the LIM interaction domain entirely, LDB1::KMT2A - the clearest statement in this literature that a sarcoma fusion keeps KMT2A exons 4 to 36 and discards exons 1 to 3, The menin interface is a requirement of 5'-KMT2A fusions in haematopoiesis, not of KMT2A rearrangement as such - and a solid tumour has been quietly proving it for six years
217. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39633542
     Complete remission of NUP98 fusion-positive acute myeloid leukemia with the covalent menin inhibitor BMF-219, icovamenib

     Carraway HE, et al. · Haematologica 110(4):1041-1046 2025
     used by Evicting the fusion is not enough: PRC1.1 has to arrive, and losing it causes menin-inhibitor resistance in vivo, Icovamenib (BMF-219) — the covalent menin inhibitor that left oncology for diabetes, In NUP98-rearranged leukaemia, who responds to a menin inhibitor is decided by the co-mutations, not by the fusion, NUP98 is an eligibility criterion in 22 of 57 menin-inhibitor trials including a paediatric trial for that genotype alone - and NSD1 and KDM5A appear in none of them, so trials select on the fusion and never on its partner, The first published complete remission of NUP98-rearranged AML on a menin inhibitor (icovamenib/BMF-219, n=1)
218. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 39700011
     Protocol for CRISPR-Cas9-mediated induction of KMT2A rearrangements in cell line and umbilical cord blood hematopoietic stem and progenitor cells

     Benz T, Larghero P, Meyer C, et al. · STAR protocols 2025
     used by Experiment: bait the KMT2A breakpoint cluster region and sequence everything it joins to, in a fetal-like human progenitor, The test bed nobody names: KMT2A rearrangement can be induced and counted in primary human CD34+ and fetal liver stem cells, and it happens without any drug at all
219. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40232843
     Genetic inactivation of FAAP100 causes Fanconi anemia due to disruption of the monoubiquitin ligase core complex.

     Kuehl J, Xue Y, Yuan F, Ramanagoudr-Bhojappa R, Pickel S, Kalb R, Chandrasekharappa SC, Wang W, Zhang Y, Schindler D · J Clin Invest 2025
     used by FAAP100 — FA core complex; rank 36 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all
220. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39922194
     The phenylalanine-and-glycine repeats of NUP98 oncofusions form condensates that selectively partition transcriptional coactivators

     Ahn JH, et al. · Molecular Cell 85(4):708-725.e9 2025
     used by Five KMT2A-free NUP98 fusions bind MLL1 and the NSL complex — and one unbiased mass-spectrometry study failed to reproduce it, No proximity, degron or tiling-CRISPR study has ever been run on WRAD in KMT2A-fusion leukaemia, NUP98 FG condensates, audited assay by assay: no half-bleach has ever been done and no NUP98 fusion has ever been endogenously tagged, Re-bound at full text, where methods live: 20 records pair a WRAD subunit with a proximity-labelling method and a KMT2A term, 14 pair one with a tiling-CRISPR term, and none is a proximity, degron or tiling study of WRAD in a KMT2A-fusion line, Settle the WRAD question: tagged co-IP plus degron-timed proximity across three fusion classes, The nuclear pore and NUP98 fusions — a fusion that takes a pore protein's disordered repeats off the pore and builds nuclear droplets with them, Verdict on the WRAD contradiction: the graph is right, its citation class is wrong, and its universal is wrong, WRAD reaches KMT2A fusions only as a passenger on a recruited wild-type complex
221. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     GRAFAPEX (treosulfan) for injection - US prescribing information, dosage regimen table (NDA 214759; SPL set id 2d06b03c-17aa-0492-e063-6294a90abd8f)

     Medexus Pharma, Inc.; US Food and Drug Administration · openFDA Drug Label API, api.fda.gov 2025
     used by Fludarabine - the immunosuppressive half of modern conditioning, given as a phosphate prodrug, cleared by the kidney, and dosed by a body-surface-area rule that measurably fails in children, Treosulfan - a European conditioning standard for three decades that the FDA first approved in January 2025, for a diagnosis and an age that exclude the infant with KMT2A-rearranged ALL
222. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39841459
     GATA2 links stemness to chemotherapy resistance in acute myeloid leukemia

     Alikarami F, Xie HM, Riedel SS, Goodrow HT, Barrett DR, Mahdavi L, Lenard A, Chen C, et al. · Blood 145:2179-2195 2025
     used by GATA2 - the least KMT2A-selective gene on this beat, ranking 17,591 of 17,728, and a factor whose leukaemia biology is about stemness and chemoresistance rather than about the fusion
223. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40421803
     The role of multivalency in the association of the eight twenty-one protein 2 (ETO2) with the nucleosome remodeling and deacetylase (NuRD) complex.

     Dan-Dukor G, Shang S, Leighton GO, Travis CR, Schwochert TD, Agrawal P, Ajasa O, Li T, Waters ML, Ginder GD, Williams DC · Nucleic Acids Research 2025
     used by GATAD2A / p66-alpha (Q86YP4) - the subunit that bridges NuRD's two modules, the best-ranked NuRD gene in this project's KMT2A-selectivity scan, and present in the pan-fusion interactome under MLL-AF9 but NOT the index fusion
224. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40825195
     Epigenetic changes by EZH2 inhibition increase translocations in B cells with high AID activity or DNA repair deficiency.

     Tao J, Alessandri L, Gasparetto A, Zhao L, Zhang X, Alt FW, et al. · Blood 2025
     used by Giving a translocation-promoting epigenetic drug in a translocation-defined B-lineage leukaemia, to infants, H3K27me3 - the repressive mark this graph argued about for seventy-seven cycles without ever writing an entry for it
225. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40111261
     Discovery of Novel SIK2/3 Inhibitors for the Potential Treatment of MEF2C+ Acute Myeloid Leukemia (AML)

     Zhu W, Zhao P, Liu T, Gao F, Li Q, Cai X, Zhang M, Aliper A, Ren F, Zhavoronkov A, Ding X · Journal of Medicinal Chemistry 68:7518-7538 2025
     used by Giving the reopening conditions an owner, and the first run changes two decisions (run)
226. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40957893
     Gephyrin filaments represent the molecular basis of inhibitory postsynaptic densities.

     Macha A, Liebsch F, Bruckisch EHW, Burdina N, von Stülpnagel I, Benting K, et al. · Nat Commun 2025
     used by GPHN (gephyrin) — synaptic scaffold and molybdenum-cofactor enzyme, KMT2A fusion partner in t(11;14)(q23;q24)
227. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40185404
     High Melphalan Exposure Increases the Risk of Graft-Versus-Host Disease in Pediatric Patients Undergoing Alpha-Beta T-Cell Depleted Haploidentical Transplantation.

     Dvorak CC, Cho S, Salinas Cisneros G, Higham CS, Chu J, Winestone LE, Temple WC, Kharbanda S, et al. · Transplantation and Cellular Therapy 2025
     used by Graft-versus-host disease in a transplanted infant - the only antileukaemic benefit and the main cause of death are the same process at different grades, Melphalan - the third agent in Interfant-06 conditioning, dosed per square metre in babies who are dosed per kilogram for everything else in the same week, Weight or surface area - the Interfant-06 conditioning week uses both units in eight days, and the one measured correction in the literature went the wrong way
228. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40102405
     Guanine nucleotide biosynthesis blockade impairs MLL complex formation and sensitizes leukemias to menin inhibition.

     Shi X, Li M, Liu Z, ..., Nakada D · Nat Commun 2025
     used by Guanine nucleotide supply sustains the LEDGF/menin/MLL-fusion complex - the one place in this graph where metabolism sits UPSTREAM of the menin interface, IMPDH2 - the rate-limiting guanine-nucleotide enzyme whose inhibition lowers LEDGF and menin protein and dismantles the MLL-fusion complex itself, Is the metabolic phenotype a consequence of the fusion programme or an independent dependency? The answer is that BOTH directions are published, and one of them points the other way entirely, LEDGF occupancy under revumenib: the measurement the graph called missing exists, in one 2025 preprint, and it goes the way the tenfold cooperativity predicts, Repurposing approved IMPDH inhibitors (mycophenolate, mizoribine, ribavirin) in KMT2A-rearranged leukaemia - cheap, mechanistically attractive, and asking an immunosuppressant of a neutropenic infant, The clearest clinical rationale for a LEDGF agent - second line after menin-inhibitor failure - has never been tested, and one 2025 measurement now argues against it, The KMT2A-fusion causal chain: six links, one measured ordering, and two arms that are parallel rather than sequential, You can lower LEDGF without a LEDGF ligand: its protein half-life is about 4 hours against a proteome average of 20, so blocking guanine nucleotide or rRNA synthesis takes it out first
229. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40713835
     Histone H4 lysine 20 methylation marks genes dynamically regulated during erythroid maturation

     Murphy K, Getman M, Lv X, et al. · Epigenetics & Chromatin 2025
     used by H4K20me1 - the transcription- and replication-linked H4 state, whose gene-body level tracks Pol II; it HAS been profiled genome-wide in human haematopoietic stem cells twice, and a query scoped to 'leukemia' cannot see either dataset
230. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41291235
     Histone demethylase KDM9 activates the CCND1/AKT pathway to promote the malignant progression of gliomas through interaction with BRD2.

     Cheng J, et al. · Cell Mol Life Sci 2025
     used by H4K20me2 - the abundant repair-linked H4 mark, the 53BP1 docking site, and the first H4K20 state in this graph; never once measured in a KMT2A-rearranged cell, RSBN1 / KDM9 (Q5VWQ0) - an H4K20me2/me3 demethylase in the AFF4 proximity record, and the only read-queue partner that is a chromatin enzyme at all
231. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 40373471
     The synergy of TPL and selinexor in MLL-R acute myeloid leukemia via Rap1/Raf/MEK pathway-mediated MYC downregulation.

     Deng M, Huang P, Wang L, et al. · Translational Oncology 2025
     used by Has anyone tested an XPO1 inhibitor in a KMT2A-rearranged system? Yes - four preclinical studies and zero clinical ones, counted with the queries and the controls, Selinexor (XPO1 inhibition) — a real paediatric response rate attached to an unproven mechanism in KMT2A-rearranged disease
232. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 40340946
     Innovative evaluation of selinexor and JQ1 synergy in leukemia therapy via C-MYC inhibition.

     Wang PH, Hu CH, Fan JQ, et al. · Journal of Translational Medicine 2025
     used by Has anyone tested an XPO1 inhibitor in a KMT2A-rearranged system? Yes - four preclinical studies and zero clinical ones, counted with the queries and the controls
233. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus cell line HB11;19 (CVCL_8227)

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by HB11;19 (CVCL_8227) is KMT2A::MLLT1, not KMT2A::AFF1 — and it is the most menin-dependent line in the panel
234. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40966497
     SMRT anchors the HDAC3 corepressor complex to chromatin to regulate inflammatory and metabolic pathways in macrophages.

     Efthymiadou A; Gu C; Wang C; Wang H; Li Z; Garcia-Irigoyen O; Fan R; Treuter E; Huang Z · Nucleic Acids Res 2025
     used by HDAC3 - the only HDAC in this disease whose requirement was established genetically rather than by a drug, and the same experiment shows it is not fusion-specific
235. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.journal-articlePMID 41249257
     Selective HDAC6 inhibitor WT161 modulates the VLA-4/FAK pathway by inhibiting PKA activity in acute lymphoblastic leukemia

     · Sci Rep 15(1):40178 2025
     used by HDAC6 - the one HDAC family member this graph refused, whose refusal named a falsifier that has been in the literature since 2020 and fires in the index fusion's own cell line
236. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40967435
     Inhibition of HDAC7 reprograms the histone H3.3 landscape to induce heterochromatin spreading and DNA replication defects in cancer cells.

     Hassan O, et al. · J Biol Chem 2025;301:110732 2025
     used by HDAC7 - the eraser the index fusion silences, where the proposed therapy is to INDUCE the HDAC, and two 2024-2025 papers point in opposite directions
237. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41093075
     Sp100A isoform promotes localization of the histone chaperone HIRA to PML nuclear bodies.

     Della Fera AN, Arman W, Powers ME, et al. · Journal of Biological Chemistry 2025
     used by HIRA - the chaperone that puts new H3.3 into transcribed gene bodies, and therefore the machine that runs this graph's clearance clock
238. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39844759
     H2-K1 protects murine MLL-AF9 leukemia stem cells from natural killer cell-mediated immune surveillance.

     Ghosh S, Rodriguez-Zabala M, Dushime GT, Reinbach K, Ramakrishnan R, Sitnicka E, Jaras M · Haematologica 2025
     used by HLA-A - the class I heavy chain a menin inhibitor was actually measured on, and the human orthologue of the MHC class I molecule that protects MLL-AF9 leukaemia stem cells from NK cells, In this fusion family, MHC class I is not silenced - it is elevated and load-bearing, holding NK cells off the leukaemia stem cell, Raising MHC class I is not a free good: the same molecule is the inhibitory ligand that holds NK cells off, and in this fusion family it is an in vivo leukaemia dependency, The missing measurement: is MHC class I bivalent, does a menin inhibitor raise it, and does raising it cost NK control - in a KMT2A-rearranged cell, for the first time, The NK cell - the effector arm of haploidentical transplant, the one this disease is documented to evade, and the cell CLEC12A was named on
239. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 39626355
     TIFAB modulates metabolic pathways in KMT2A::MLLT3-induced AML through HNF4A.

     Wang Y, Xiu Y, ..., Zhao C · Blood Adv 2025
     used by HNF4A - a liver and pancreas nuclear receptor acting as the metabolic effector of TIFAB in KMT2A::MLLT3 AML, on a single paper, Is TIFAB a direct RelB target? Two papers in the same MLL-AF9 system answer differently, TIFAB — a 161-residue NF-kB adaptor-layer protein with TWO direct KMT2A-fusion papers, which is more disease-specific evidence than any receptor or TRAF in this beat has
240. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 39745610
     Using the Conserved Hexapeptide in HOX Proteins as an Antagonist of HOX/PBX Interactions

     Morgan R, Smith C, Pandha H · Methods in Molecular Biology 2889:139-153 2025
     used by HOXA10 - named in 27 entries as part of the HOXA output and never written; a posterior HOX paralogue that is regulated with HOXA9 and tested far less often, The HOX-PBX interface, and its one peptide: HXR9/HTL001 has been tried in eight tumour types and in KMT2A-rearranged leukaemia exactly once
241. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40451434
     The transcription factor HOXA9 induces expression of the chromatin modifier SMYD3 to drive leukemogenesis.

     Zhang L, Zhong J, Yang L, et al. · J Biol Chem 2025
     used by HOXA9 — required for survival of established MLL-rearranged leukemia, and dispensable for starting it, SMYD3 - a lysine methyltransferase with three claimed histone marks and one robust non-histone substrate, sitting on an HOXA9 feed-forward loop in MLL-AF9 AML and a fatty-acid-oxidation axis in CML stem cells, with zero interventional trials
242. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 41062506
     The genomic landscape of relapsed infant and childhood KMT2A-rearranged acute leukemia

     Ahlgren L, ... Hagstrom-Andersson AK · Nature Communications 2025
     used by Hypothesis: the KMT2A genomic breakpoint carries prognostic information that the field has been sitting on for twenty years, IKZF1 - the defining co-lesion of every other high-risk B-ALL, and this disease does not use it until after treatment, No infant or childhood KMT2A-rearranged cohort has REPORTED IDH status — and at least one has certainly MEASURED it, No second driver means no second target - the quiet genome forecloses the combination logic that works in every other leukaemia, NR3C1 - the receptor the single most prognostic drug in this disease acts through, and the fusion suppresses it, Open ground: the questions in this graph that nobody in the landscape appears to be working on, Subclonal cooperating lesions lost at relapse - what was actually measured, and why 'lost' is the wrong word, The cohort paper this graph said had certainly measured IDH status was opened: 96,537 characters of full text contain IDH1 zero times, IDH2 zero times, TET2 zero times and DNMT3A zero times, so the measured-not-reported class is confirmed by reading rather than by inference, The second ring — smaller KMT2A-fusion mechanism labs, and where the literature actually points, TP53 - named in 84 entries of this graph, absent from the index genome study of the disease, and four different things depending on when you look
243. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40016386
     Menin inhibitor MI-503 exhibits potent anti-cancer activity in osteosarcoma.

     Tian S, Hao ZY, Xu DH, Wang XZ, Shi CC, Zhang Y · Sci Rep 2025
     used by Hypothesis: the menin-MLL complex writes the same mark onto two address lists with opposite cell-state outputs, and which one a tissue reads decides whether blocking menin is a therapy or a lesion, Menin's other address list: the same complex that switches on HOXA in blood writes H3K4 methylation onto the CDK inhibitors p27 and p18 in endocrine cells
244. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40045344
     Bone marrow sympathetic neuropathy is a hallmark of hematopoietic malignancies and it involves severe ultrastructural damage

     Bernal A, Cuminetti V, Serulla M, Florit A, Konieczny J, Golnarnik G, Chen Y, Ferre M, et al. · Experimental Hematology and Oncology 2025
     used by Hypothesis: treatment-remodelled niche, not niche-imposed dormancy, is what residual KMT2A-rearranged disease exploits, MLL-AF9 leukaemia destroys the nerves that run its own niche — a mechanism class this graph had nothing on, Sympathetic nerve fibre in bone marrow — the wiring that sets the niche's daily rhythm, through beta-3 in health and beta-2 in leukaemia
245. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41015030
     IGF2BP3 redirects glycolytic flux to promote one-carbon metabolism and RNA methylation

     · Cell Reports 2025
     used by IGF2BP3 — an RNA-binding protein required for MLL-Af4 leukaemogenesis in mice that CRISPR barely touches in human lines
246. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus cell line IMSUTi002-A-2 (CVCL_C9HE)

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by IMSUTi002-A-2 (CVCL_C9HE) — a doxycycline-inducible KMT2A::AFF1 iPSC line, and the isogenic design nobody in this graph has used
247. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40341256
     Regulation of H3K4me3 breadth and MYC expression by the SETD1B catalytic domain in MLL-rearranged leukemia

     Izumi S, Ohtani K, Matsumoto M, Shibata S, Rahmutulla B, Fukuyo M, Nishimoto M, Miyagawa H, Sakaida E, Yokote K, Kitabayashi I, Araki K, Kaneda A, Hoshii T · Leukemia 39(7):1627-1639 2025
     used by Interactome round 5: 42 queries, 13 entries written, 9 candidates rejected with counts, and four alias failures of four different kinds, MYC - named in a hundred entries of this graph and, until now, written in none, SETD1B - the COMPASS paralogue round 4 deferred for want of a leukaemia paper, which had already been published: its SET domain sets H3K4me3 breadth and MYC in MLL-rearranged AML, WDR5 is partitioned, not shared: NSL and SET1/MLL complexes compete for one pool, so perturbing NSL changes how much WDR5 reaches the wild-type KMT2A complex the fusion depends on
248. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40270205
     S-adenosylmethionine addiction confers sensitivity to methionine restriction in KMT2A-rearranged acute lymphoblastic leukemia.

     Tee T, Ruiter TJJ, Wu S, ..., Van Leeuwen FN · Haematologica 2025
     used by Is the metabolic phenotype a consequence of the fusion programme or an independent dependency? The answer is that BOTH directions are published, and one of them points the other way entirely, MAT2A - the enzyme that makes the methyl donor, and the one metabolic dependency in this disease with two independent papers and a lymphoid PDX result, SAM / methionine dependence - the one metabolic state in this graph demonstrated in KMT2A-rearranged lymphoblastic leukaemia itself, with a drug and a PDX behind it, SAM supply sustains the KMT2A-rearranged hypermethylated state - the metabolic requirement that IS a consequence of the chromatin programme, and can be attacked as one
249. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40472028
     Jund orchestrates cis-regulatory element dynamics to facilitate endothelial-to-hematopoietic transition.

     Guo J, Liu M, Liu F, Wang L · Proc Natl Acad Sci U S A 2025
     used by JUND - the AP-1 subunit menin holds down, and the one a menin inhibitor lets go
250. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 39965267
     Cancer-associated mutation at glycine 400 in TIP60 disrupt its phase separation property and catalytic activity resulting in compromised DNA damage repair function of the cell.

     Gupta H, Singh A, Gupta A · Biochem Biophys Res Commun 2025;753:151457 2025
     used by KAT5 / Tip60 - the acetyltransferase in the only direct KMT2A-fusion histone-variant result, and both fusions tested were myeloid
251. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40830799
     KAT6A chimeras form a self-reinforcing epigenetic module with NURF and MLL/COMPASS to sustain AML

     · Genome Biology 2025
     used by KAT6A / MOZ — the acetyltransferase that is a fusion oncogene in its own right
252. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40536321
     Histone Demethylase UTX Suppresses Tumor Cell Proliferation by Regulating Stress Granules.

     Liu X; Liu X; Xue M; Xiao Y; Chen Y; Qiu R; Wu D; Zhou Y; Wang J; Yuan Y; Yu L; Shi T; Li Y; Su H; Chen H; Liu Y; Huang K; Zheng L · Adv Sci (Weinh) 2025
     used by KDM6A / UTX — a commonly asserted KMT2A partner that belongs to a different complex and points the opposite way
253. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40646135
     Ontogeny-specific induction of the KMT2A::AFF1-fusion drives development of a distinct CD24 positive pre-leukemic state.

     Calderón AS, Ghazanfari R, et al. · Leukemia 2025
     used by KMT2A::AFF1 needs a developmental window and a lymphoid-committed cell — the cell type is a condition of transformation, not a consequence of it, The CD24-positive pre-leukaemic state — what the index fusion makes before it makes leukaemia, The neonatal window — the state in which an MLL fusion can transform, bounded at both ends
254. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41121446
     KMT2A alterations in acute myeloid leukemia: a proposed genetic risk model and transplantation outcomes.

     Chen L, Li J, et al. · Exp Hematol Oncol 2025
     used by KMT2A::ELL in adult AML: the one partner that separates, in two independent adult cohorts, The comutation confound: KRAS, DNMT3A, TP53 and KMT2A-PTD track with partner and carry prognostic weight of their own
255. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40879670
     Type B3 Thymoma With a Novel KMT2A::MAML3 Fusion: Expanding the Spectrum of Gene Fusions Beyond the MAML2 Gene.

     Zhou Z, Yu Y, Chen C, Lin J · Genes, Chromosomes & Cancer 2025
     used by KMT2A::MAML2 keeps MAML2's activation domain and loses its Notch-binding domain, and suppresses Notch output, KMT2A::MAML2 type B2/B3 thymoma - the same fusion, a different organ, a different disease, KMT2A::MAML2, inv(11)(q21q23) - a therapy-related fusion that also causes a solid tumour, MAML2 exon 2: the strongly preferred 3' acceptor, the same in leukaemia, thymoma and salivary-gland tumours
256. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41402159
     Advancing diagnostic targeted RNA sequencing for haematological malignancies within an Australian sample exchange program.

     Li EW, Tiong IS, Gould C, Catalano A, Aung H, Seymour L, White D, Thompson E, Blombery P, Iland H, Wright D · Pathology 2025
     used by KMT2A::USP2 is invisible to karyotype and often to FISH, so these patients are misclassified as fusion-negative
257. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 41189082
     Dual KMT2A::USP2 and CBL::GRIK4 Fusions in Infant-Type B-ALL: A Case Report.

     Du C, Zhang N, Xia M, Jiang L, Weng W · Pediatric Blood & Cancer 2025
     used by KMT2A::USP2, inv(11)(q23.3q23.3) - the minor-BCR fusion that keeps the PHD fingers
258. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 40628245
     Venetoclax-Based Regimen in Refractory or Relapsed Pediatric Acute Lymphoblastic Leukemia.

     Zhang L, Zhang Z, Lu A, Jia Y, Huang L, Zhang L, Zeng H · Acta Haematologica 2025
     used by KMT2A::USP2, inv(11)(q23.3q23.3) - the minor-BCR fusion that keeps the PHD fingers
259. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39806204
     Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

     Wang N, Pachai MR, Li D, et al. · Nat Genet 2025
     used by KMT2C (MLL3) - the fetal brake on MLL-rearranged leukaemia, and a 7q tumour suppressor chemotherapy selects against, Re-bound at full text: still nobody has asked whether a KMT2A fusion GAINS chromatin sites under a menin inhibitor - but the data to ask it are now deposited, 158 ChIP-seq samples including spike-in-normalised FLAG-MLLAF9 under VTP50469, so the class moves from never-measured to measured-not-analysed, The MLL3/4-UTX switch fails to throw — menin inhibition kills by turning something ON, and cells that cannot turn it on survive
260. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 40016188
     Targeting osteoclasts for treatment of high-risk B-cell acute lymphoblastic leukemia.

     Kotecha RS, Trinder SM, Hughes AM, Mullin BH, Rashid S, Yuan J, et al. · Blood Cancer J 2025
     used by Kotecha group, Perth: the infant KMT2A-rearranged laboratory this graph had cited once, Zoledronic acid against the osteoclast: a bone-marrow-niche target, but not tested in infant KMT2A-rearranged disease
261. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     KOMZIFTI (ziftomenib) US prescribing information, INDICATIONS AND USAGE, retrieved via the openFDA drug label API

     US Food and Drug Administration; Kura Oncology, Inc. · openFDA drug label API 2025
     used by Kura Oncology — ziftomenib (KO-539): an adults-only sponsor that quietly supplies infant trials
262. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39721581
     LDB1 establishes multi-enhancer networks to regulate gene expression

     Aboreden NG, Lam JC, Goel VY, et al. · Molecular Cell 2025
     used by LDB1::KMT2A - the clearest statement in this literature that a sarcoma fusion keeps KMT2A exons 4 to 36 and discards exons 1 to 3
263. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40857670
     LEF1 intragenic deletion induces a dominant-negative isoform and unveils a Wnt/β-catenin vulnerability in T-ALL.

     Delafoy M, Bonnet MF, Lengliné E, Cieslak A, et al. (17 authors; Asnafi V senior author) · Blood 2025
     used by LEF1 — the Wnt/β-catenin DNA-binding factor of the T-lineage, named as an MLL-AF4-specific interactor in a T-ALL cell line and with essentially no B-lineage or KMT2A literature
264. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 41333696
     Blinatumomab-Related Lineage Switch of KMT2A/AFF1-Rearranged B-Lymphoblastic Leukemia to B/Myeloid Mixed-Phenotype Acute Leukemia and Myeloid Sarcoma Causing Spinal Cord Compression

     Fan X, Gupta A, Dabrowski D, Rusella M, Zhai QJ, et al. · Case Reports in Hematology 2025
     used by Lineage switch as antigen escape from CD19-directed therapy in KMT2A-rearranged leukemia, Where KMT2A-rearranged leukemia physically sits — marrow niche, CNS, blood, liver/spleen and skin
265. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40579588
     Multipotent lineage potential in B cell acute lymphoblastic leukemia is associated with distinct cellular origins and clinical features

     Iacobucci I, Zeng AGX, Gao Q, Garcia-Prat L, Baviskar P, et al. · Nature Cancer 2025
     used by Lineage switch in KMT2A-rearranged leukemia — the same clone changes what kind of blood cell it is
266. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40907896
     Ubiquitin-specific protease 7 promotes the growth and oncogenic potential of acute myeloid leukemia cells through the deubiquitination and upregulation of LRRK2.

     Park JH, Chung KC · J Biol Chem 2025
     used by LRRK2 - the AFF4 row is one of 78 hits on an in-vitro protein array, but the protein has a real AML literature that arrived through USP7 and interferon, not through the interactome, USP7 - the enzyme that holds PRC1.1 together, and the only pharmacological handle on this complex that exists today
267. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 40856631
     A novel MAP7D1 mutation causes mitotic defects and RPS14 accumulation in Shwachman-Diamond syndrome patient cells.

     Kucukvardar S, Karabay A · Dis Model Mech 2025
     used by MAP7D1 (Q3KQU3) - the strongest index-fusion p-value of the nine deferred pan-MLL-fusion preys, on a protein UniProt places entirely outside the nucleus
268. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40341856
     Downregulation of SENP1 impairs nuclear condensation of MEF2C and deteriorates ischemic cardiomyopathy.

     Xie Y, et al. · Clin Transl Med 2025;15:e70318 2025
     used by MEF2C — an output-program transcription factor, the second-strongest leukemia co-dependency, and a gene humans cannot spare one copy of
269. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39907684
     Targeted inhibition of menin promotes beta-catenin-mediated GLP-1 expression and improves glucose tolerance in high-fat diet-induced obese mice.

     Cao X, Yu L, Zhang Q, Cheng Z, Meng H, Wang C, et al. · FASEB Journal 2025
     used by Menin inhibition in the gut, not the islet: MI-463 raises GLP-1 from intestinal L cells, Three extra tubes: the glucose study that answers the inversion in children
270. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39817905
     Menin orchestrates macrophage reprogramming to maintain the pulmonary immune homeostasis.

     Zhu X, Xu B, Lian A, Zhang X, Wang Y, Zhang Y, Zhang L, Ma J, Gao S, Jin G · Cell Rep 2025
     used by Menin-SETD2, mapped to the NTD and Palm and tooled with a peptide at menin 231-248: the third partner assigned to the same half of menin, and the writer arm of the HR scaffold
271. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39789150
     Lactylation modulation identifies key biomarkers and therapeutic targets in KMT2A-rearranged AML.

     Liu D, Liu S, Ji Y, ..., Ma X · Sci Rep 2025
     used by Metabolic enzyme enumeration in KMT2A-rearranged leukaemia: the instrument, its positive controls, seventeen bounded absences - and the counted zero that would have been wrong
272. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 40921261
     KMT2A-rearranged leukemia: from mechanism to drug development

     Ernst P, ... Yokoyama A · Experimental Hematology 2025
     used by Michael Cleary (Stanford) & Akihiko Yokoyama (National Cancer Center, Tsuruoka) — the groups that discovered the menin requirement itself, Patricia Ernst (University of Colorado) — what normal KMT2A and menin actually do, which is the therapeutic-window question
273. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 40332046
     Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study

     · Blood 2025
     used by Model: predicting who responds to a menin inhibitor - no patient-level data is public, so this cannot be trained either, NPM1 (nucleophosmin) — the nucleolar shuttle whose mutant form binds chromatin with KMT2A and buys the second menin-inhibitor indication, Revumenib (SNDX-5613, Revuforj) — first approved menin–KMT2A interface inhibitor
274. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 40584390
     Moving the Needle in KMT2A Rearranged Pediatric B-Cell Acute Lymphoblastic Leukemia: Newer agents and novel approaches.

     Ray A, Jain A, Vijayaran M, et al. · Clin Hematol Int 2025
     used by MRD as a trial endpoint in KMT2A-rearranged leukaemia: high negativity rates, and almost none of them say which assay, The Interfant-06 backbone, phase by phase: what the protocol every infant reference in this graph points at actually does
275. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40373211
     Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease

     Musunuru K, et al. · New England Journal of Medicine 2025
     used by N-of-1 and n-of-few: the custom-therapy route, and what it actually costs
276. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39774774
     Endogenous CD4+ T Cells That Recognize ALK and the NPM1::ALK Fusion Protein Can Be Expanded from Human Peripheral Blood.

     Stadler S, Blasco RB, Singh VK, et al. · Cancer Immunol Res 2025
     used by No junction-specific antibody exists for any KMT2A fusion - and synovial sarcoma shows exactly what one would buy
277. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
     A Phase 1a/1b Study of the Safety, Pharmacokinetics, and Antitumor Activity of the Oral Menin Inhibitor Ziftomenib in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) After Imatinib Failure

     Kura Oncology, Inc. · ClinicalTrials.gov 2025
     used by No menin inhibitor has ever enrolled a KMT2A-rearranged solid tumour, and the one solid-tumour menin trial that read out was terminated for lack of efficacy
278. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40561247
     Posttranscriptional depletion of ribosome biogenesis factors engenders therapeutic vulnerabilities in NPM1-mutant AML

     Damaskou A, Wilson R, Gozdecka M, Giotopoulos G, et al. · Blood 146(10):1239-1252 2025
     used by NPM1 (nucleophosmin) — the nucleolar shuttle whose mutant form binds chromatin with KMT2A and buys the second menin-inhibitor indication
279. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.preprintPMID 41279818
     ZMYND11 Restrains KMT2A to Enable a Neuronal Developmental Program

     Greben AW, Wu XS, Robb JE, Vogel IR, et al. · bioRxiv 2025
     used by NSD1 - the H3K36 dimethyltransferase whose catalytic activity a NUP98 fusion cannot do without, and which cells can otherwise lose almost for free, Three blots and one drug curve: does the ZMYND11::MBTD1 fusion protein still bind KMT2A, and does a menin inhibitor work in a leukaemia with no KMT2A rearrangement, ZMYND11 (BS69) - an H3.3K36me3 reader that restrains elongation, is itself the 5' partner of a chromatin-hijacking AML fusion driving HOXA/MEIS1/MYB, and whose promoter is the third-strongest MLL1-N bin in RS4;11, ZMYND11::MBTD1 AML is menin-inhibitor sensitive despite having no KMT2A rearrangement, because the translocation deletes ZMYND11's MYND domain and with it a physical brake on wild-type KMT2A, ZMYND11::MBTD1 is the KMT2A-fusion architecture assembled from different parts - and the part it throws away is a direct physical brake on KMT2A itself
280. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40263434
     Loss of NOL10 leads to impaired disease progression of NUP98::DDX10 leukemia

     Shima Y, et al. · Leukemia 39(6):1368-1379 2025
     used by NUP98::DDX10, inv(11)(p15q22) — the 'helicase' fusion whose helicase activity turns out not to be the point
281. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40115133
     Challenging the prognostic expectations: a rare case of ZNF618::NUTM1-positive B-cell lymphoblastic leukemia with poor outcome

     Chen X, Yuan L, Ma X, et al. · Blood Science 2025
     used by NUTM1-rearranged B-ALL - the KMT2A-wild-type arm of the same infant trials, with 4-year EFS of 100% against 36-37% next door
282. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 40437770
     Revumenib for Relapsed or Refractory Acute Leukemia With a KMT2A Translocation

     · Ann Pharmacother 2025
     used by Of 62 registered menin- or DOT1L-inhibitor trials, 7 have stopped and none gave a safety reason - four were company or supply decisions - yet the same drugs carry dose-limiting differentiation syndrome and QT prolongation that the registry never mentions, Revumenib (SNDX-5613, Revuforj) — first approved menin–KMT2A interface inhibitor, Syndax Pharmaceuticals — revumenib (SNDX-5613), the only menin inhibitor licensed down to infancy
283. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
     Human Protein Atlas subcellular location table (v25 download, Last-Modified 2025-11-06)

     · Human Protein Atlas 2025
     used by Only BRD4 (mitotic chromosome) and CHD4 (mitotic spindle) of 31 fusion-pathway proteins carry the Human Protein Atlas cell-cycle flag (3.5% of all proteins), and the flag, defined by localisation to mitotic structures, does not mark TOP2A, a canonical G2/M gene, The Human Protein Atlas lists AFF1 as mitochondrial and nucleoplasmic at only 'Approved' reliability, with mitochondria as the single-cell-variable compartment, against nucleoplasm for KMT2A, menin and most of the pathway - a localisation lead that needs an orthogonal check
284. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Prescription Drug User Fee Rates for Fiscal Year 2026

     US Food and Drug Administration · Federal Register, doc. 2025-14413, 30 July 2025 2025
     used by Orphan drug designation: what it actually gives a KMT2A programme, and what it bends
285. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.news
     Kura Oncology and Kyowa Kirin Announce FDA Approval of KOMZIFTI (ziftomenib), the First and Only Once-Daily Targeted Therapy for Adults with Relapsed or Refractory NPM1-Mutated Acute Myeloid Leukemia

     Kura Oncology, Inc. and Kyowa Kirin Co., Ltd. · Kura Oncology investor relations 2025
     used by Orphan drug designation: what it actually gives a KMT2A programme, and what it bends
286. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 40243620
     Modulation of the ETV6::RUNX1 Gene Fusion Prevalence in Newborns by Corticosteroid Use During Pregnancy

     Benitez L, Fischer U, Crispi F, et al., Bueno C, Menendez P, Borkhardt A, Gratacos E · International Journal of Molecular Sciences 2025
     used by Pablo Menendez & Clara Bueno (Josep Carreras Leukemia Research Institute, Barcelona) — cellular origin, fetal models and infant-specific drug resistance
287. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40108441
     Pbx3-mediated suppression of type I interferon response contributes to leukemia progression driven by MLL-AF9.

     Tang L, Lu M, Du Y, Sun J · Cancer Gene Ther 2025
     used by PBX3 - the TALE cofactor the field says is non-redundant, and the experiment that says HOXA9 is the redundant one
288. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39137448
     A Refined Population Pharmacokinetic Model-Based Guideline for Individualized PEGasparaginase Dosing in Pediatric Acute Lymphoblastic Leukemia.

     Brigitha LJ, Zaky K, Pieters R, van der Sluis IM · Ther Drug Monit 2025
     used by Pegaspargase - the same enzyme wearing a polymer, dosed in units that are not the other product's units, and now dosed to a level in every group except infants
289. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus cell line PER-485 (CVCL_W984)

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by PER-485 (CVCL_W984) — the relapse half of a matched infant t(4;11) pair, and it has lost CD19
290. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus cell line PER-490 (CVCL_W986)

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by PER-490 (CVCL_W986) — a KMT2A::AFF1 B-ALL line from a nine-day-old infant
291. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus ages resolved by DepMap cross-reference for ACH-000045, ACH-000113, ACH-000146, ACH-000168, ACH-000362, ACH-000782, ACH-000874, ACH-001574, ACH-001647, ACH-001735, ACH-001736

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by PER-490 (CVCL_W986) — a KMT2A::AFF1 B-ALL line from a nine-day-old infant
292. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus cell line PER-494 (CVCL_A8JU)

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by PER-494 (CVCL_A8JU) — infant t(4;11;7) line, and the one whose AFF1 was never demonstrated
293. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus cell line PER-785 (CVCL_IZ03)

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by PER-785 (CVCL_IZ03) — infant t(4;11) line from a child who survived
294. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40788108
     Energy Deficiency-Induced ATG4B Nuclear Translocation Inhibits PRMT1-Mediated DNA Repair and Promotes Leukemia Progression.

     Wang Z, Zhang X, Zhou Y, Lin S, Fu Y, Liu H, Gao Q, Xiao Y, Yin Z, Liu S, Huang K, Deng S, Du J, Zeng H, Wang J, Zheng J, Zhou Q, Chen T, Gao X, Ju Z, Liu B · Adv Sci (Weinh) 2025
     used by PRMT1 — an MLL-fusion cofactor whose first-in-human inhibitor was terminated for lack of efficacy and toxicity
295. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     Cellosaurus DR (cross-reference) fields for CVCL_0095, CVCL_0093, CVCL_0064, CVCL_1069, CVCL_W986, CVCL_W984, CVCL_A8JU, CVCL_IZ03, CVCL_3993, CVCL_6867, CVCL_3994, CVCL_3995, CVCL_QW47, CVCL_7125

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by PRoXe — the one leukaemia xenograft repository that is actually public, and what that buys
296. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 39633556
     Depletion of the RNA binding protein QKI and circular RNA dysregulation in T-cell acute lymphoblastic leukemia.

     Buratin A, Palhais B, Gaffo E, et al. · Haematologica 2025
     used by QKI - a KMT2A proximity row in K562, and a tumour suppressor whose loss concentrates in the HOXA subtype of T-ALL
297. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39774844
     Targeting senescent stemlike subpopulations in Philadelphia chromosome-like acute lymphoblastic leukemia

     Ding YY, Sussman JH, Madden K, Loftus JP, Chen RK, Falkenstein CD, et al., Tasian SK · Blood 2025
     used by Quiescence (G0) — the state 15 entries invoke to explain measurable residual disease, defined here for the first time
298. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40913148
     Phase separation of ERCC6L2-CtIP regulates the extent of DNA end resection.

     · Nat Cell Biol 2025
     used by RBBP8 / CtIP - the only unwritten core-complex partner with a DIRECT-interaction record, and the graph already held its mechanism without holding the protein
299. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40435410
     RBM15-MKL1 fusion protein promotes leukemia via m6A methylation and Wnt pathway activation

     Mayday MY, et al. · Blood 2025
     used by RBM15 — m6A adaptor, AMKL fusion partner, and a named hit in the only KMT2A-biased RNA-protein CRISPR screen
300. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.preprintPMID 41279410
     IGF2BP3 remodels the microRNA targeting landscape in MLL-AF4 leukemia

     Kabbani LES, et al. · bioRxiv 2025
     used by RNA-binding proteins set how much KMT2A::AFF1 protein a cell makes from its own fusion transcript, The RNA layer and the menin interface are separable: IGF2BP3 depletion sensitises MLL-AF4 leukaemia to menin inhibition and outperformed it alone
301. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41059649
     RRP12 Variants Are Associated With Autosomal Recessive Brain Calcifications.

     Monfrini E, Rinchetti P, Anheim M, Klingseisen A, Lagha-Boukbiza O, Cen Z, Yang D, Chen X, Maroofian R, Houlden H, Cappelletti G, Richard AC, Quenez O, Toro C, Frucht SJ, Lotti F, Luo W, Hunt D, Nicolas G, Riboldi GM · Mov Disord 2025
     used by RRP12 (Q5JTH9) - a pre-40S export factor in six of seven MLL-fusion interactomes but NOT in the index fusion's, and the block's only member with a recessive human disease published in 2025
302. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40073106
     RTF1 mediates epigenetic control of Th17 cell differentiation via H2B monoubiquitination.

     Galan C, Lu G, Gill R, Li D, Liu Y, Huh JR, Hang S · J Immunol 2025
     used by RTF1 — the PAF1C subunit the graph was missing, on a complex that does bind the retained KMT2A fragment, Th17 cell - the mature CD4 T-helper subset whose differentiation and maintenance require MENIN, which makes it the clearest published on-target normal-tissue liability of the menin interface
303. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40729681
     Enhancer heterogeneity in acute lymphoblastic leukemia drives differential gene expression in patients

     Smith AL, Denny N, Chahrour C, Sharp K, Arachi M, Dopico-Fernandez AM, et al. · Blood 2025
     used by RUNX2 - a direct KMT2A-chimera target and dependency in T-ALL, a patient-specific enhancer target in KMT2A::AFF1 B-ALL, and the gene a menin inhibitor represses to restore steroid sensitivity in t(4;11) infants
304. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 40501411
     Metabolic epigenome targeting hits KMT2A-rearranged acute lymphoblastic leukemia.

     Heckl D, Rettinger E · Haematologica 2025
     used by SAM supply sustains the KMT2A-rearranged hypermethylated state - the metabolic requirement that IS a consequence of the chromatin programme, and can be attacked as one
305. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus cell line SCMC-L1 (CVCL_7125)

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by SCMC-L1 (CVCL_7125) — a four-month-old's KMT2A::AFF1 line carrying NSD2 E1099K
306. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus records for RS4;11 (CVCL_0093) and KOCL-45 (CVCL_3993) — NSD2 p.Glu1099Lys annotations

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by SCMC-L1 (CVCL_7125) — a four-month-old's KMT2A::AFF1 line carrying NSD2 E1099K
307. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 39634129
     SET-NUP214-induced hypermethylation landscape promotes abnormal overexpression of HOXC cluster genes in acute megakaryoblastic leukemia.

     Kaushal A, et al. · Genes Dis 2025
     used by SET::NUP214 has no address of its own: chromatin-bound CRM1 is already at HOX, and the fusion's FG repeats dock onto it
308. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40263296
     Targeting oncogenic activation of FLT3/SREBP/FASN promotes the therapeutic effect of quizartinib involving disruption of mitochondrial phospholipids.

     Yin F, Yang J, Luo H, Yu T, Lu W, Zhao M, Du H, Wen S, Huang P, Hu Y · Cell Death Dis 2025
     used by SREBF1 / SREBP-1 - the weakest of the three MEN1 sterol partners, because it is simultaneously the pathway's readout
309. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41094145
     A conserved H3K14ub-driven H3K9me3 for chromatin compartmentalization.

     Huang Y, Sun Y, Qi H, Jiang Q, et al. · Nature 2025
     used by SUV39H1 (O43463, KMT1A) - the H3K9me3 writer: a menin effector whose binding region OVERLAPS the drug pocket at its N-terminus, a tumour suppressor in MLL-AF9 AML, recruited to double-strand breaks by CTCF, and never localised at the KMT2A locus in any cell type
310. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40391410
     TCF3::ZNF384 induces steroid resistance in B-cell precursor acute lymphoblastic leukemia cells.

     Kusano S, Ueno-Yokohata H, Hori M, Ishibashi T, Fujimura J, Shimizu T, Ohki K, Kiyokawa N · Pediatr Int 2025
     used by TCF3::ZNF384 - the partner whose contribution is now actually demonstrated: steroid resistance, and it is not shared with EP300::ZNF384, The necessary lesion in ZNF384-rearranged leukaemia is LOSS of the ZNF384 C-terminus, not GAIN of a fusion partner, The ZNF384 family is not the inverse of KMT2A::AFF1 - it is the SAME grammar written in the opposite gene order, and three of the four claims in the inverse framing are false
311. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40530668
     KRAS mutation status critically determines the clinical outcome of patients with KMT2A-rearranged acute myeloid leukemia.

     Wu Y, Yuan X, et al. · Cancer 2025
     used by The comutation confound: KRAS, DNMT3A, TP53 and KMT2A-PTD track with partner and carry prognostic weight of their own
312. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40263763
     Baseline Characteristics of Parents Enrolled in Children's Oncology Group Study ACCL20N1CD: Financial Toxicity During Treatment for Pediatric Acute Lymphoblastic Leukemia in the United States

     Santacroce SJ, Beauchemin MP, Ponce O, et al. · Pediatric Blood & Cancer 2025
     used by The cost the hospital never sees: half of families spend more than 15% of their income
313. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     Class waivers

     European Medicines Agency, Paediatric Committee · EMA 2025
     used by The EU paediatric investigation plan: an obligation, not an incentive - and the deferral is the loophole
314. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40389585
     Highly specific Immunoproteasome inhibitor M3258 induces proteotoxic stress and apoptosis in KMT2A::AFF1 driven acute lymphoblastic leukemia.

     Jenkins TW, Fitzgerald JE, Park J, et al. · Scientific reports 2025
     used by The five verdicts in one place, plus what this beat read and did not use
315. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41274245
     Development of a CRISPR/Cas9-degron system that enables in vivo specific gene depletion in leukemia models.

     Shimura R, Yamamoto K, Chang YH, et al. · Biochemical and biophysical research communications 2025
     used by The five verdicts in one place, plus what this beat read and did not use
316. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40089994
     Single-cell panleukemia signatures of HSPC-like blasts predict drug response and clinical outcome

     Chen C, Xu J, Sussman JH, et al. (senior author Tan K) · Blood 2025
     used by The HSPC-like blast fraction — a minority of blasts that transcriptionally resemble haematopoietic stem and progenitor cells, found in the blood of the youngest KMT2A-rearranged patients and predicting drug response and outcome across leukaemia subtypes, The relapse-initiating persister state — present at diagnosis, identifiable before a single dose is given, and defined by basal glucocorticoid-response activation plus small size plus quiescence
317. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39587259
     A multiomic atlas identifies a treatment-resistant, bone marrow progenitor-like cell population in T cell acute lymphoblastic leukemia

     Xu J, Chen C, Sussman JH, et al. (senior author Teachey DT) · Nature Cancer 2025
     used by The HSPC-like blast fraction — a minority of blasts that transcriptionally resemble haematopoietic stem and progenitor cells, found in the blood of the youngest KMT2A-rearranged patients and predicting drug response and outcome across leukaemia subtypes
318. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus cell lines KOCL-45 (CVCL_3993), KOCL-48 (CVCL_6867), KOCL-58 (CVCL_3994) and KOCL-69 (CVCL_3995)

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by The KOCL series (CVCL_3993, CVCL_6867, CVCL_3994, CVCL_3995) — four Japanese infant KMT2A::AFF1 lines, all under one year
319. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
     Cellosaurus cell line KOCL-48 (CVCL_6867)

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by The KOCL series (CVCL_3993, CVCL_6867, CVCL_3994, CVCL_3995) — four Japanese infant KMT2A::AFF1 lines, all under one year
320. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     Births in England and Wales: 2024

     Office for National Statistics · Office for National Statistics 2025
     used by The national scale: about 24 infants a year in England and Wales, about 12 in Australia
321. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     Births, Australia, 2024

     Australian Bureau of Statistics · Australian Bureau of Statistics 2025
     used by The national scale: about 24 infants a year in England and Wales, about 12 in Australia
322. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.preprintPMID 40161712
     Fetal context conveys heritable protection against MLL-rearranged leukemia that depends on MLL3.

     Mendoza-Castrejon J, Yang W, et al. · bioRxiv : the preprint server for biology 2025
     used by The neonatal window — the state in which an MLL fusion can transform, bounded at both ends
323. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Fee Rate for Using a Priority Review Voucher in Fiscal Year 2026

     US Food and Drug Administration · Federal Register, doc. 2025-18075, 18 September 2025 2025
     used by The rare paediatric disease priority review voucher: a $150-200m bearer bond, lapsed for 14 months, now live to 2029
324. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.news
     Abeona Therapeutics Closes Sale of Rare Pediatric Disease Priority Review Voucher for $155 Million

     Abeona Therapeutics Inc. · Abeona Therapeutics investor relations 2025
     used by The rare paediatric disease priority review voucher: a $150-200m bearer bond, lapsed for 14 months, now live to 2029
325. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39602342
     Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUM.

     Kalwak K, Moser LM, Poetschger U, Bader P, Kleinschmidt K, Meisel R, Dalle JH, Yesilipek A, et al. · Blood Advances 2025
     used by Thiotepa - the third agent that reaches the central nervous system completely, and whose alkylating metabolites are excreted through the skin into a nappy, Treosulfan - a European conditioning standard for three decades that the FDA first approved in January 2025, for a diagnosis and an age that exclude the infant with KMT2A-rearranged ALL
326. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.preprintPMID 40196700
     TP53 Inactivation Confers Resistance to the Menin Inhibitor Revumenib in Acute Myeloid Leukemia.

     D'Souza J, Leung CJ, Ballapuram AC, et al. · bioRxiv 2025
     used by TP53 - named in 84 entries of this graph, absent from the index genome study of the disease, and four different things depending on when you look, TP53 inactivation and the apoptotic threshold — the drug still switches the program off, and the cell still does not die
327. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus ages and same-individual relationships resolved by DepMap cross-reference for the eleven-line KMT2A-rearranged panel

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by Verdict: 'eleven cell lines, none infant-derived' is right about the screen and wrong about the material — at least ten infant KMT2A::AFF1 lines exist
328. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Cellosaurus search API: q=KMT2A-AFF1 (29 records) and per-line identifier lookups for PER-490, PER-485, PER-494, PER-785, PER-784, PER-826, PER-703, PER-910

     Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
     used by Verdict: 'eleven cell lines, none infant-derived' is right about the screen and wrong about the material — at least ten infant KMT2A::AFF1 lines exist
329. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39840526
     Nuclear Condensates of WW Domain-Containing Adaptor With Coiled-Coil Regulate Mitophagy via Alternative Splicing.

     Wang J, Fan Y, Luo G, Xiong L, Wang L, Wu Z, Wang J, Peng Z, Rosen CJ, Lu K, Jing J, Yuan Q, Zhang Z, Zhou C · Adv Sci (Weinh) 2025
     used by WAC — the adaptor that hands RNF20/RNF40 to RNA polymerase II, and the only member of this axis whose knockdown alone killed MLL-rearranged ALL cells
330. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40677927
     Whole Genome Sequencing of "Mutation-Negative" Individuals With Cornelia de Lange Syndrome.

     Ansari M, Halachev M, Parry D, Campos JL, D'Souza EN, Barnett C, Wilkie AOM, Barnicoat A, Patel CV, Sukarova-Angelovska E, Girisha KM, Firth HV, Prescott K, Wilson LC, McEntagart M, Davidson R, Lynch SA, Joss S, Holden ST, Lam WK, et al. · Hum Mutat 2025
     used by WDR18 (Q9BV38) - the Rix1/PELP1-TEX10-WDR18 60S maturation subunit, in five MLL-fusion interactomes but NOT the index fusion's, and the block's only member whose nucleolar partitioning is SUMO-controlled
331. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40958680
     The MLL/WDR5 complex promotes midbody recruitment of KIF2C for microtubule depolymerization and furrow initiation during cytokinesis.

     Kataria A, Hemalatha N, Chinchole A, Tyagi S · J Cell Sci 2025
     used by WDR5 and KMT2A are at the centrosome and the midbody - a non-chromatin address for both, with a patient-cell phenotype
332. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.news
     Wholesale Acquisition Cost Information for Colorado Prescribers: REVUFORJ (revumenib)

     Syndax Pharmaceuticals, Inc. · Syndax Pharmaceuticals (state-mandated disclosure) 2025
     used by What a menin inhibitor costs: the list price, worked out for an infant
333. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39962500
     Exploring the financial burden of pediatric bone marrow transplantation: a cross-sectional study from the caregiver's viewpoint

     Soodi O, Abdollahiasl A, Amini S, Hesari E · BMC Health Services Research 2025
     used by What a transplant costs: about $276,000 for the admission alone
334. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40536430
     KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia

     Michmerhuizen NL, et al. · Cancer Discovery 15(10):2096-2116 2025
     used by Why a nucleoporin fusion needs menin-MLL1: the second menin-dependent fusion family, and what it borrows rather than carries
335. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40997022
     Inhibition of XPO1 by selinexor enhances terminal erythroid maturation through modulation of HSP70 trafficking in severe β0-thalassemia/HbE.

     Khamphikham P, Tantiworawit A, Anuchapreeda S · PLoS One 2025
     used by XPO1 / exportin-1 (CRM1) - the cell's main nuclear export receptor, and a chromatin-bound transcriptional scaffold
336. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 40437414
     Targeting EP300 in diffuse large b-cell lymphoma: efficacy of A485 and synergistic effects with XPO1 inhibition.

     Jiang Y, Xing D, He X, et al. · BMC Cancer 2025
     used by XPO1 / exportin-1 (CRM1) - the cell's main nuclear export receptor, and a chromatin-bound transcriptional scaffold
337. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 39887933
     Nuclear to Cytoplasmic Transport Is a Druggable Dependency in HDAC7-driven Small Cell Lung Cancer.

     Qin T, Wang J, Wang J, et al. · Adv Sci (Weinh) 2025
     used by XPO1 / exportin-1 (CRM1) - the cell's main nuclear export receptor, and a chromatin-bound transcriptional scaffold
338. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 40712110
     CNS Involvement by North American-Adult T-cell Leukemia/Lymphoma Is Associated With Discrete Dissemination Patterns and Molecular Profiles, Involving XPO1 E571 and KLF2/PI3KCD in Selected Cases.

     Shah N, et al. · JCO Precision Oncology 2025
     used by XPO1 E571K: a change-of-function hot spot in the NES-binding groove - and it does NOT confer resistance to the drugs that bind the same groove
339. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 40780498
     ZC3H13 facilitates the progression of acute myeloid leukemia through m6A-FOXP1-mediated metabolic reprogramming

     Wang J, et al. · Exp Hematol 2025
     used by ZC3H13 — the m6A writer subunit with the most evenly KMT2A-selective dependency signal in the panel, and almost no literature
340. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.regulatory
     FDA approves ziftomenib for relapsed or refractory acute myeloid leukemia with a NPM1 mutation

     US Food and Drug Administration · FDA Oncology (Cancer) Approval Notifications 2025
     used by Ziftomenib (KO-539, Komzifti) — once-daily menin inhibitor approved in NPM1-mutant AML
341. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39093982
     NG2 is a target gene of MLL-AF4 and underlies glucocorticoid resistance in MLLr B-ALL by regulating NR3C1 expression.

     · Blood 2024
     used by 'Not expressed on normal haematopoietic cells' is a claim about blood, and it has been read for thirty years as a claim about the body, Cell-surface capture proteomics on an isogenic human KMT2A::AFF1 model against its matched normal progenitor - the experiment an mRNA screen cannot replace, CSPG4 / NG2 - the flow-cytometry surrogate for a broken KMT2A, and a direct target gene of the fusion that makes it, Does the diagnostic marker survive the drug? Surface NG2, CD133, CD10 and CD33 under menin and DOT1L inhibition, with the rearrangement held fixed, ITGA4 (VLA-4) and NG2 — the niche-adhesion axis of KMT2A-rearranged B-ALL, and the one approved drug that hits it, NG2 in KMT2A-rearranged patients replicates in two independent TARGET profiles - 3 of 4 and 9 of 13 above the 90th percentile of everyone else - but it is bimodal, and the 552-fold median ratio I first computed is an artefact of a near-zero denominator, NG2 reads the fusion's transcriptional programme, not the DNA lesion - so a menin inhibitor should erase the graph's best diagnostic marker while the rearrangement stays put, NG2/CSPG4 is the one antigen in the whole surfaceome that KMT2A::AFF1 itself drives - and it is a pericyte and vascular protein, at 124.5 nTPM in normal blood vessel and 246 TPM in tibial artery, NR3C1 - the receptor the single most prognostic drug in this disease acts through, and the fusion suppresses it, Of every antigen this project names, only NG2, LAMP5 and CD123 are present on all three KMT2A::AFF1 cell lines - CD19 is at 0.2 nTPM in MV4-11 and CD33 at 2.3 in RS4;11, Pablo Menendez & Clara Bueno (Josep Carreras Leukemia Research Institute, Barcelona) — cellular origin, fetal models and infant-specific drug resistance, Pre-B cell — the stage KMT2A::AFF1 leukaemia never reaches, and why that boundary is informative, Pro-B cell — the stage at which KMT2A::AFF1 leukaemia is arrested, and the phenotype the diagnosis is made on, REFUTED IN THE CYCLE IT WAS WRITTEN - the proposal that fusion-driven and normal-tissue-clean surface antigens are disjoint in KMT2A::AFF1 because of what the fusion's output programme is; an expression-matched permutation says it is the base rate, The pro-B arrest state — what a KMT2A::AFF1 blast is actually doing while it sits there, What an immunophenotype can and cannot tell you about a genotype - the arithmetic of a surrogate marker, worked on NG2
342. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 39419001
     Transcriptional memory formation: Battles between transcription factors and repressive chromatin.

     Zhao Z, Zhu B · Cell Syst 2024
     used by 'Transcriptional memory' means two different things in this literature, and both of them are used about MLL leukaemia
343. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 39472576
     MLL oncoprotein levels influence leukemia lineage identities

     Janssens DH, Duran M, Otto DJ, Wu W, Xu Y, Kirkey D, Mullighan CG, Yi JS, Meshinchi S, Sarthy JF, Ahmad K, Henikoff S · Nature Communications 15:9341 2024
     used by 148752 and 152985 are one patient before and during revumenib, not two treated patients - so the drug-free arm this corpus said did not exist is sample 148752, 42% of every gene-body occupancy call is at a locus where wild-type MLL1 is also bound - but the AFF1-exclusive class is not, HOXA9 and MEIS1 are not, and SPAG7 is, A GEO cell-type field can name the patient's clinical course rather than the aliquot's exposure, and the two readings differ by an entire control arm, A pre-registered, institution-matched serial-pair replication: does a patient's own target set predict itself better than another child's does?, A quantile calling rule and an absolute one answer different questions, and on the same data they can order the same pairs oppositely, A second sample id is not a second patient: three of the interesting pairs in GSE252378 are one patient twice, and reading them as independent doubles the apparent n, A statistic whose denominator contains its numerator cannot test a magnitude claim, and the tell is that its between-sample spread sits near 1 whatever the biology does, A target map read off the diagnostic sample does not describe the same child's disease after a lineage switch, Across one infant's B-ALL to AML lineage switch, HOXA occupancy collapses ~28-fold and IRX1 falls only ~2.2-fold, AFF1 and fusion occupancy transfer between infants at Spearman 0.82-0.92, but H3K4me3 transfers better at 0.93-0.97 - so the transferable part is mostly promoter structure, not fusion targeting, AFF1 occupancy does not distinguish fusion-occupied promoters from wild-type KMT2A promoters in primary infant KMT2A::AFF1 - reproduced at promoter resolution, and the corpus should stop reading a partner ChIP as a fusion readout, AFF1-exclusivity describes 378 of 719 genes and 72% of them rest on one patient - and the MEIS1 comparison I used to call IRX1 indistinguishable was an artefact of scoring MEIS1 with the weaker instrument, Applied symmetrically, the criteria that were never applied make IRX1 the weakest member of the class it won - and MEIS1, a canonical fusion target, is indistinguishable from it, so the deposit cannot separate the two, At promoter resolution the published N/C oncoprotein criterion calls 1043 promoters in fusion-negative CD34+ HSPCs - above the median across 27 KMT2A-rearranged patients - while the same-reagent controls in that sample call 66 and 11, Between-patient variation in oncoprotein occupancy is not a fusion-partner effect: across six partners the within-partner range of the amplitude statistic is as wide as the between-partner range of its medians, Bounded absence: every chromatin measurement under a menin inhibitor is in an adult-derived line, and none is in an infant KMT2A::AFF1 model, Bounded absence: no published study has tested whether a KMT2A fusion GAINS chromatin sites under a menin inhibitor - and the same pipelines found gains for two other proteins when they looked, Census of every published chromatin-occupancy measurement made under a menin inhibitor: eight datasets, every one TSS-anchored, every one tabulating losses only, Depth matching changes this pair's call counts by under one percent, so library depth is not what separated the two beats - a candidate explanation cleared, Drug exposure and clonal replacement are completely confounded across this pair - the relapse sample is a different clone in a different lineage, and the paper's own reading is that the drug killed the cells the diagnostic sample was made of, ENL is the only elongation cofactor that separates fusion-occupied promoters from wild-type KMT2A promoters by more than the H3K4me3 negative control does, in primary infant KMT2A::AFF1, ENL stays after the fusion leaves — an epigenetic lesion that outlives the protein that made it, Experiment: a 6 / 24 / 72 hour / 7 day VTP-50469 time course in SEM reading menin occupancy and H3K4me3 together, to decide whether the 23% is a partial effect or a slow one, Experiment: endogenously tagged KMT2A::AFF1 imaged through a menin-inhibitor time course, with a five-compartment segmentation and a half-life arm, Experiment: five-fraction subcellular blot of a t(4;11) line, with a menin-inhibitor arm - converting thirty years of unattributable images into attributable numbers using only existing antibodies, Flow-cytometric MRD: the fastest readout, and the one a lineage switch walks straight out of, For AFF1 in primary infant material, which antibody you use moves the answer more than which patient, which lineage, or cell line versus patient - a pre-registered falsifier that fired, GEO labels both aliquots of the lineage-switching patient 'treated with the Menin inhibitor', but the paper says 148752 is the B-ALL at diagnosis and only 152985 arose during treatment - the deposit's drug flag is a case label wearing an aliquot label's clothes, GMP-like state — the destination of therapy-driven lineage switch and, separately, the state most sensitive to menin inhibition, Granulocyte-monocyte progenitor (GMP) — the committed cell an MLL fusion can turn back into a stem cell, GSE252378 contains menin CUT&RUN in exactly one patient - a KMT2A::ENL lineage-switching pair under a menin inhibitor - and none in any of its eight KMT2A::AFF1 patients, GSE252378 fragment BEDs: a complete KMT2A N-terminal / C-terminal antibody set in 27 patient samples across six fusion partners, deposited and until now unopened by this corpus, GSE252378 holds the only AFF1 CUT&RUN in primary KMT2A::AFF1 patient material - four libraries across two patients, three disease states and the SEM cell line, all hg38, GSE252378 labels one of its two SEM AFF1 libraries KMT2A-AFF2, a fusion that does not exist in the deposit and does not exist in SEM - a filter on that field silently halves the SEM data, H3K4me3 is by far the most reproducible track in primary infant leukaemia CUT&Tag - replicate rho 0.97-0.98 - which makes it both the assay's proof of competence and the benchmark that every fusion-site enrichment should be quoted against, HOXA occupancy is the partner-invariant: occupied in 17 of 18 non-AFF1 KMT2A-r samples, 2.94x to 29.1x, HOXA9/HOXA10 is unoccupied and unmethylated at H3K4 in two of the three primary infant KMT2A::AFF1 states, while the SEM cell line carries the strongest AFF1 signal over that locus of any sample in the deposit, Hypothesis: a defined subset of fusion binding sites survives saturating menin inhibition on menin-independent tethering, and that residual set is where bypass resistance comes from, Hypothesis: menin inhibition does not clear the fusion from chromatin but redistributes it onto the four fifths of the unmethylated CpG address it normally ignores, Hypothesis: menin inhibition does not merely displace KMT2A::AFF1 from chromatin, it destabilises it — the evicted fusion is degraded, not parked, Hypothesis: menin inhibition pushes cells toward the GMP-like state, and the GMP-like state is where menin inhibition works best — so a lineage switch on therapy should predict response, not failure, Hypothesis: the HOXA-negative, IRX1-negative KMT2A-rearranged blast is a low-oncoprotein-dosage state, not a state whose oncoprotein has been redirected to another programme, Hypothesis: the three quarters of H3K4me3 that survive menin displacement at fusion target sites are held by a menin-independent complex, and identifying it names the combination partner for a menin inhibitor, If the target promoter set is no more conserved within a patient than between patients, then nothing in the oncoprotein complex remembers the first disease, In a patient, the menin-fusion association is demonstrable before the drug and unmeasurable after it - and the asymmetry is what this pair establishes, not a rate of menin loss, In an unsupervised 5 kb correlation of 41 SEM libraries, both KMT2A N-terminal AutoCUT&RUN libraries have menin as their single nearest neighbour - the menin-interface hypothesis appearing as the top-level structure of an analysis that was not looking for it, In drug-naive primary infant KMT2A::MLLT1 B-ALL, menin is as enriched as the fusion N-terminus at the top fusion promoters (2.73x vs 3.12x over an accessibility reference) while the wild-type C-terminal reporter sits at background (1.10x), In the HOXA-dead infant states IRX1 carries H3K4me3 and ENL while HOXA9/HOXA10 carry neither, In the revumenib-exposed relapse sample nothing is enriched above a non-specific reference - not menin, not the fusion N-terminus, not ENL - and the sample's own top-ranked promoters are mitochondrial pseudogenes, Independent positive control: of 27 samples, the ONE that calls zero oncoprotein-target promoters is 152985 - the AML that arose during menin-inhibitor treatment, which the paper reports as having oncoprotein and menin reduced to undetectable levels, IRX1 occupancy is a lineage-switch cell state, and in GSE252378 it is confounded with the AFF1 partner and one institution, IRX2 IS fusion-occupied at gene-body scale in p454 - and q151's promoter-scale zero of 27 turns on one replicate 5% below the threshold, which two other instruments put above it, King verification of Q154: the AFF1-exclusive target class survives every stratification and a different seed, and IRX1 individually does not - the partner signal is real at the class level and gone at the gene level, Lineage switch as a menin-inhibitor escape route — documented in a patient on revumenib, and invisible to every resistance-mutation screen, Menin inhibition is a reshuffle, not a subtraction: four proteins are documented to GAIN chromatin or persist under the drug, and none of them is the fusion, Most gene-body 'AFF1-exclusive' calls in GSE252378 are a fold-change threshold cutting an oncoprotein-level gradient - and IRX1 is the one member where the non-AFF1 samples are genuinely at background, Of the 58 two-patient AFF1-exclusive genes, four - not one - are called exclusive by both instruments, and the surviving IRX1 claim does not beat a patient-level null (p=0.092) [CORRECTED by q171], On one universe with one rule and a structure-respecting null, the two lineages of one infant overlap no more than two unrelated KMT2A::AFF1 infants do, p279 and p318: one infant, two diseases, and an oncoprotein target map that does not carry over, Partner-exclusivity does discriminate: of four comparator partner groups only AFDN fires, it is 4-of-4 AML, and lineage-matching collapses it to exactly chance while AFF1's class survives the same restriction, Partner-protein occupancy is not fusion occupancy: every KMT2A::AFF1 chromatin claim resting on an AFF1, AFF4 or SEC-subunit ChIP is an upper bound that includes free complex, Pooling the two AF4 antibodies, as the published analysis does, drops AFF1's fusion-site enrichment from 1.8-4.6x the null to 0.8-2.1x - below the H3K4me3 negative control in all three samples, POST HOC: against institution-matched, anchored comparators the same-patient pair has the LOWEST excess in all six factorial cells - which leans to q142, but was not pre-registered, q142's exact comparison - p279 against its own switched AML versus p279 against an unrelated infant - replicates in q144's own universe with q144's own rule, and q144 never made it, Recalibrate the N/C oncoprotein threshold on the fusion-negative CD34+ control at the interval scale it will actually be used at, and report the false-positive count at every scale rather than one, Run on the reciprocal KMT2A-C antibody instead of the fusion-side KMT2A-N, the same rule gives zero AFF1-exclusive recurrent gene bodies against a null of 0.52 - the gene-scale class is fusion-arm specific, SEM, the standard t(4;11) model line, has zero signal at IRX1 — every model of this disease is a model of one subgroup, Settle the monocytic confound isogenically: degrade the fusion, read haem-gene dependency before lineage has time to move, Six gene bodies are AFF1-exclusive and recurrent at gene scale; the authors' own pipeline confirms one of them, refutes three and has never measured two - and IRX1 is the one it confirms, Swap the AFF1 C-terminus onto a KMT2A-AF9 backbone and score IRX1 occupancy: the direct test of partner causality, TB051939 is rank 12 of 26 and owns fewer singletons than its even share; the library that owns 22.4% of singletons destroys no exclusivity at all; and dropping any single comparator moves the exclusive set by a median of 2 genes, The '0.400, keeps 1,894 of 2,045 calls' in the dispatch brief is two independent per-sample call counts read as a retention ratio; the intersection is 1,116 of a 2,812 union, The 17-promoter AFF1-only recurrent core is not more recurrence than a label permutation of the same matrix gives, The AML-over-ALL retention ratio is 93.5% denominator: the GMP-like numerator barely moves across 23 samples while the B-lineage denominator varies fourteenfold, so the ratio measures loss of the B-lineage class and not gain of the GMP-like one, The B-ALL and the AML of one infant share no more fusion-occupied promoters than two unrelated infants do - lineage, not patient identity, sets where KMT2A::AFF1 sits, The CD34+ oncoprotein-negative sample that calibrates the published N/C threshold is in GSE159608, not GSE252378 - so the 1.75 threshold cannot be re-derived from the deposit that carries the 27 patients it is applied to, The compound in the only infant menin-inhibitor occupancy sample is revumenib, named in the abstract - and neither the dose nor the duration of exposure is recorded in the paper, the GEO record or the authors' repository, The coverage guard withheld 30 of 351 pairs and named every one: 26 contain 152985, which calls zero promoters, and a Jaccard with a zero-call sample is a division, not a measurement, The deposit paper's own supplementary table calls IRX1 an oncoprotein target in exactly p279, p318 and p454 - the same three samples this project reached by a different instrument, The deposit's two lineage-switching patients behave in opposite directions: the untreated pair keeps 1126 of its 2045 oncoprotein-target promoters across the switch, while the menin-inhibited pair falls from 345 to zero - so lineage switching does not by itself clear the oncoprotein, The excess overlap survives a structure-respecting null in both beats - permutation p = 0.0005 in all six cells - but every published excess figure shrinks 2.4- to 4-fold, The GMP-like peak class is fusion-enriched in exactly one of GSE252378's 27 KMT2A-rearranged samples - p318, the sample it was derived from - once the null is matched on how coverable those promoters generically are, The HOXA-negative, IRX1-negative KMT2A-rearranged blast, The KMT2A::AFF1 oncoprotein-target promoter set is a fusion-level property, and patient identity adds nothing measurable on top of it, The lineage-switched AML state of infant KMT2A::AFF1, described by chromatin rather than by flow cytometry - fusion retained on PAX5 and MEIS1, lost from EBF1 and HOXA, myeloid promoters gained by DOT1L and ENL, The menin interface cannot be what decides where KMT2A::AFF1 sits: within one patient the fusion's target promoters were almost entirely replaced while the menin-binding motif was unchanged, The menin interface is identical in all 27 of these patients and the amount of chromatin their oncoproteins occupy differs by up to two orders of magnitude - so the interface can be a permission for binding but cannot be what sets how much binding happens, The menin-dependence test I proposed in the cycle-146 log cannot fire by construction - and what the one pair CAN answer is that 85% of gene-body occupancy is menin-dependent while histone clusters preferentially survive, The oncoprotein-target site count for sample 148752 is 46, 345 or 745 depending on the interval set and the universe, and the corpus has been quoting one of the three with no label, The permutation cycle 155 asked for: the two-instrument exclusive intersection is four genes not one, 34 of the 42 could never have been in it, and the surviving IRX1 claim gives p=0.092 against a patient-level null, The pre-registered magnitude test failed because the statistic was bounded by construction - top-decile share spreads only 1.1-1.4x between samples and cannot express what the published oncoprotein score says varies, The pre-registered three-branch test of 'the HOXA-negative blast's oncoprotein is on the GMP programme' returns NEITHER/UNINFORMATIVE, on four independent gates, The published peak classes do transfer from 20 kb peaks to 2 kb promoters - the GMP-over-B-lineage ratio swings 8.56-fold across the pair that defined them - but only in the between-sample direction the classes were built in, The reciprocal-antibody ratio splits the six-gene AFF1-exclusive class in two: H3C15 and SPAG7 sit at or below background, the three most enriched are the three the authors' caller says are not exclusive, and IRX1 is the only member that is both, The state under menin inhibition — differentiation in AML, rapid death in ALL, and a GMP-like exit in the cells that switch lineage instead, The taspase-1 N/C antibody control separates fusion-occupied from wild-type KMT2A promoters in every primary infant sample, and it is the C-terminal arm that does the work while being the less reproducible arm, The two beats' opposite answers are produced by the calling rule, not by the promoter universe: three universes give one answer, two rules give two, The two instruments' opposite verdicts decompose: the CALLER explains the 16-fold magnitude gap and the UNIVERSE explains the patient-level survival - and inside the shared universe the only gene both call AFF1-exclusive is IRX1, The unbounded oncoprotein score spans 1.73-12.32 log2 units within a sample - it is not the compressed statistic q142 was stuck with - and the pre-registered magnitude verdict is STILL void, because the score's amplitude is no larger than the disagreement between two antibodies against the same end of KMT2A, Thirteen of q152's seventeen AFF1-only core promoters are absent from the deposit paper's whole target-gene table, and the four that are present are AFF1-exclusive there too, Two of the nineteen non-AFF1 samples are menin-inhibitor treated, so the specificity arm is effectively seventeen - and removing them does not rescue the core, Under revumenib the oncoprotein leaves chromatin globally, so 'does IRX1 become a menin-inhibitor escape route' cannot be answered from this deposit, When one infant's KMT2A::AFF1 B-ALL became an AML, EBF1 lost fusion occupancy and PAX5 kept it - the B-lineage transcription-factor programme is not vacated as a block, Where does the fusion go when menin inhibition evicts it? Almost nobody has looked - the published readouts are chromatin occupancy, the one protein whose fate was measured properly is menin, and the single human observation of fusion loss is confounded by a lineage switch, WITHDRAWN: I identified the promoter-matrix column mean as library coverage and called A73051 depth-confounded; the column mean is the enrichment fraction, A73051 is at the 37th-39th percentile of true depth, and the share-versus-depth correlation is negative
344. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     GSE252378_family.soft.gz - the per-sample SOFT records for GSE252378, read raw with line numbers

     Janssens DH et al. · NCBI GEO FTP 2024
     used by 148752 and 152985 are one patient before and during revumenib, not two treated patients - so the drug-free arm this corpus said did not exist is sample 148752, A GEO cell-type field can name the patient's clinical course rather than the aliquot's exposure, and the two readings differ by an entire control arm, Drug exposure and clonal replacement are completely confounded across this pair - the relapse sample is a different clone in a different lineage, and the paper's own reading is that the drug killed the cells the diagnostic sample was made of, Menin, ENL and DOT1L are CUT&Tag and the four KMT2A antibodies are CUT&RUN, run three weeks apart - so every menin-versus-fusion comparison in this pair crosses both assay and batch, Neither infant sample has an IgG control, and neither of their two sequencing batches contains one - so every number from this pair is confounded with chromatin accessibility, Spike-in-normalised menin CUT&RUN with paired N- and C-terminal KMT2A antibodies in an infant KMT2A::AFF1 sample, on and off drug, in the same disease state, The authors' own deposited table puts menin at 0.87 of its diagnostic-sample signal over their oncoprotein-target peaks, in the sample their text describes as having menin reduced to undetectable levels - the two statements are about different denominators, and only one of them travels, The compound in the only infant menin-inhibitor occupancy sample is revumenib, named in the abstract - and neither the dose nor the duration of exposure is recorded in the paper, the GEO record or the authors' repository, The KMT2A N-terminal antibody reports wild-type plus fusion and the C-terminal antibody reports wild-type alone - which makes an N-versus-C difference a fusion-specific readout with no tag and no engineering, The menin that matters in an infant KMT2A-rearranged leukaemia is the menin on the fusion, and the N-minus-C antibody difference can measure it in any patient sample without a tag
345. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38965370
     Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study.

     Hernández-Sánchez A, González T, et al. · Leukemia 2024
     used by 172 adults with KMT2A-r AML: translocation subtype did not predict survival, so treat all KMT2A-r as adverse, CDKN2A - one gene, two reviewed UniProt records with the same primary symbol, and a deletion that is three times rarer here than in the infant leukaemias next door, DNMT3A - an independent adverse factor in adult KMT2A-rearranged AML and conspicuously absent from paediatric disease, which is the whole finding, KMT2A::ELL in adult AML: the one partner that separates, in two independent adult cohorts, KMT2A::MLLT3 / t(9;11): the best-known partner prognosis claim, and the three cohorts that did not reproduce it, KMT2A::MLLT3 across 612 genotyped patients: myeloid at every age, but 248 of them have ALL, and 157 of those are infants, KRAS - the commonest co-mutation in a disease that has almost none, and it is usually in a minority of the cells, The comutation confound: KRAS, DNMT3A, TP53 and KMT2A-PTD track with partner and carry prognostic weight of their own, TP53 - named in 84 entries of this graph, absent from the index genome study of the disease, and four different things depending on when you look
346. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39102629
     Impact of Age on Pharmacogenomics and Treatment Outcomes of B-Cell Acute Lymphoblastic Leukemia.

     Yoshimura S, Li Z, Gocho Y, Yang W, Crews KR, Lee SHR, et al. · J Clin Oncol 2024
     used by 6-Mercaptopurine - two years of a nightly tablet whose lethal dose is a genotype, given as a liquid to a baby who cannot swallow it and must not have it with milk, Native E. coli asparaginase - the second-largest in-vitro resistance signal in infant ALL, and a different product from the pegylated one four doses later
347. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37753808
     Individualized Use of 6-Mercaptopurine in Chinese Children with ALL: A Multicenter Randomized Controlled Trial.

     Zhou Y, Wang L, Sun LR, Zhang L, Wang HM, Liu XT, et al. · Clin Pharmacol Ther 2024
     used by 6-Mercaptopurine - two years of a nightly tablet whose lethal dose is a genotype, given as a liquid to a baby who cannot swallow it and must not have it with milk
348. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 39158067
     Epigenetic regulation of noncanonical menin targets modulates menin inhibitor response in acute myeloid leukemia.

     Zhou X, Zhang Y, Lu J, et al. · Blood 2024
     used by A cell that cannot deposit H2AK119ub is still evicted normally by a menin inhibitor and silences its vacated sites less - so a fusion-occupancy pharmacodynamic marker reads FULL ENGAGEMENT in exactly the genotype that responds worst, and this is now the fourth independent reason this corpus distrusts its own candidate markers, A claim-to-paper overlap score measures where a citation's support lives, not whether it exists - so its zero is a pointer to a supplement, not a verdict against the citation, A menin inhibitor does not only take something away - it causes PRC1.1 to put something on, and the drug needs the cell's own silencing machinery to work, A time-resolved BRG1/RING1B/H2AK119ub CUT&RUN at BENC under menin inhibition - the inv(16) experiment, run on the right disease, Adaptive, non-genetic resistance — the leukemia keeps the fusion and rewires how it is maintained, Analysis (runnable): build the first correlation matrix of menin-inhibitor resistance routes, from screens and from patient cohorts, BCORL1 — the BCOR paralogue that is in the only crystal structure of the PRC1.1 core, and is the one PRC1.1 subunit nobody has tested in KMT2A-rearranged leukaemia, Bounded unreachable: the Blood supplemental table that three entries read their NLRC5 and CIITA group assignments from cannot be retrieved by ANY programmatic route - PMC serves a landing page and the publisher 403s this client - so those claims are re-readable but not re-verifiable without a human's institutional access, CIITA - the class II transactivator, a gene menin sits on, and the only antigen-presentation gene in this disease with a knockout that proves the drug acts through it, Experiment: apply all three pressures and ask whether the survivors are the same cell, Experiment: map what stays on chromatin when the menin inhibitor has done everything it can do, GMP-like state — the destination of therapy-driven lineage switch and, separately, the state most sensitive to menin inhibition, H2AK119ub - the mark every PRC1.1 claim in this graph rests on, named in fifteen entries and written in none until now, H3K79me2 reports only the DOT1L arm of a menin inhibitor's action and is blind to its PRC1.1 arm - so the mark's response is unchanged in a PCGF1 knockout even though PCGF1 loss is a published resistance mechanism, and a cell resistant through PRC1.1 loss would look fully drug-engaged by this readout, Half the PRC1.1 intersection was free all along: Zhou's locus set is a publisher supplementary table, and 159 of this graph's gene entries are in it, Hypothesis: a defined subset of fusion binding sites survives saturating menin inhibition on menin-independent tethering, and that residual set is where bypass resistance comes from, Hypothesis: a single dormant leukemia stem cell state confers cross-resistance to menin inhibition, venetoclax and T-cell engagement at once — the common-cause failure that orthogonal combination therapy assumes away, Hypothesis: genetic and non-genetic escape from menin inhibition are substitutes, so MEN1 mutations will be rare in infants and the field's resistance biomarker will fail in children, Hypothesis: only a mechanistically orthogonal partner pre-empts menin-inhibitor resistance; a second chromatin agent will not, IFNGR1 - the receptor the whole antigen-presentation mechanism runs through, and the one where low-dose interferon-gamma makes MLL-fusion leukaemia worse, Menin inhibition is a reshuffle, not a subtraction: four proteins are documented to GAIN chromatin or persist under the drug, and none of them is the fusion, Menin-bound genes are the RNA-processing and DNA-repair machinery, H2AK119ub-only genes are neuronal and developmental, and 'menin target' is therefore a much weaker label than this graph treats it as, Monocyte — the graph's most-discussed undefined cell identity, and the confound sitting under its own DepMap haem signal, MYC reactivation through PRC1.1 loss — a named, druggable bypass out of menin dependence, NLRC5 - the MHC class I transactivator, and the route by which interferon activates class I when KMT2A and KMT2B are both gone, PCGF1 — the PRC1.1 scaffold whose LOSS causes menin-inhibitor resistance, so it is a restraint on the leukaemia rather than a dependency of it, Portfolio theory — a hedge only works against uncorrelated risk, and nobody has estimated the correlation matrix of resistance routes, PRC1.1 — the complex this graph has been leaning on, now enumerated subunit by subunit, and the enumeration changes the conclusion, PRC1.1 is not both an effector and a resistance gene by coincidence: the two published readings are one activity measured from opposite ends, Q50 enumeration: every query this beat ran, every zero it recorded with its bound, and the papers it read and did not use, RYBP - the subunit that makes a variant PRC1 complex catalytically active, named by two entries in this graph and never written, The KMT2A-fusion causal chain: six links, one measured ordering, and two arms that are parallel rather than sequential, The menin/Polycomb split between NLRC5 and CIITA does not extend to their pathways, and the MHC locus is structurally invisible to the method that found it, The MHC was never invisible - the resolver was wrong - and once the classical chains are joined the class I machinery is bivalent, not unmarked, There is no selective PRC1 catalytic inhibitor - the entire chemistry is one 2013 tool compound and its analogues, and it hits both paralogues by design, Titrate PRC1.1 capacity against menin-inhibitor response, and measure H2AK119ub on the same timecourse as H3K79me2, USP7 - the enzyme that holds PRC1.1 together, and the only pharmacological handle on this complex that exists today, Venetoclax in KMT2A-rearranged leukemia — the apoptotic partner every other drug needs, When MYC falls after a menin inhibitor, there are three mechanisms it could be, and no published experiment separates them
349. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     GSE252378: AutoCUT&RUN of KMT2A-rearranged primary leukemia samples (KMT2A N- and C-terminal antibodies, ENL, DOT1L, H3K4me3, IgG)

     Janssens DH, et al. · NCBI Gene Expression Omnibus 2024
     used by A cohort median is a summary of many nulls and the null of none of them, A cross-partner absence is a rule-of-three bound, and the denominator must be the samples that could have shown it, A group of four cannot support a correlation at any effect size: name it, do not compute it, A Jaccard index is not a result until its null knows that active promoters cluster, A quantile calling rule and an absolute one answer different questions, and on the same data they can order the same pairs oppositely, A reversed genomic interval returns a plausible low number and no error — the coordinate gate caught mine, A second sample id is not a second patient: three of the interesting pairs in GSE252378 are one patient twice, and reading them as independent doubles the apparent n, A Spearman over exact zeros is tie-degenerate, and argsort-of-argsort silently picks one value from a range, A statistic whose denominator contains its numerator cannot test a magnitude claim, and the tell is that its between-sample spread sits near 1 whatever the biology does, A width-matched panel of loci that cannot be occupied is a usable per-locus floor; IgG in this deposit is not, A73051 is the one HOXA-negative non-AFF1 sample in GSE252378, and it is IRX1-negative too, Across one infant's B-ALL to AML lineage switch, HOXA occupancy collapses ~28-fold and IRX1 falls only ~2.2-fold, AFF1 and fusion occupancy transfer between infants at Spearman 0.82-0.92, but H3K4me3 transfers better at 0.93-0.97 - so the transferable part is mostly promoter structure, not fusion targeting, AFF1 occupancy does not distinguish fusion-occupied promoters from wild-type KMT2A promoters in primary infant KMT2A::AFF1 - reproduced at promoter resolution, and the corpus should stop reading a partner ChIP as a fusion readout, An anchored comparison keeps the nuisance sample on both sides, which is how you ask whether a PAIR is special rather than whether a SAMPLE is unusual, An expression subgroup is not an occupancy subgroup — and this project keeps reading one as the other, Between-patient variation in oncoprotein occupancy is not a fusion-partner effect: across six partners the within-partner range of the amplitude statistic is as wide as the between-partner range of its medians, Depth matching changes this pair's call counts by under one percent, so library depth is not what separated the two beats - a candidate explanation cleared, Eight of 27 GSE252378 samples fail a pre-registered depth or readability gate, and two of them are the only HOXA-negative non-AFF1 candidates, ENL is the only elongation cofactor that separates fusion-occupied promoters from wild-type KMT2A promoters by more than the H3K4me3 negative control does, in primary infant KMT2A::AFF1, For AFF1 in primary infant material, which antibody you use moves the answer more than which patient, which lineage, or cell line versus patient - a pre-registered falsifier that fired, GEO labels both aliquots of the lineage-switching patient 'treated with the Menin inhibitor', but the paper says 148752 is the B-ALL at diagnosis and only 152985 arose during treatment - the deposit's drug flag is a case label wearing an aliquot label's clothes, GSE252378 carries an institution-level batch effect: unrelated pairs from the same hospital overlap more than cross-hospital pairs, and a cohort-median comparator absorbs that into the same-patient claim, GSE252378 contains menin CUT&RUN in exactly one patient - a KMT2A::ENL lineage-switching pair under a menin inhibitor - and none in any of its eight KMT2A::AFF1 patients, GSE252378 contains no megakaryoblastic sample, so the 0-of-18 non-AFF1 IRX1 occupancy bound does not cover the one subgroup where IRX1 is actually expressed, GSE252378 deposits no transcriptional readout: all 171 samples are library_strategy OTHER and the metadata never says RNA, so every programme claim from this deposit is occupancy and none is expression, GSE252378 fragment BEDs: a complete KMT2A N-terminal / C-terminal antibody set in 27 patient samples across six fusion partners, deposited and until now unopened by this corpus, GSE252378 holds eight KMT2A::AFF1 oncoprotein panels from two centres, not the three this corpus had used, GSE252378 holds the only AFF1 CUT&RUN in primary KMT2A::AFF1 patient material - four libraries across two patients, three disease states and the SEM cell line, all hg38, GSE252378 labels one of its two SEM AFF1 libraries KMT2A-AFF2, a fusion that does not exist in the deposit and does not exist in SEM - a filter on that field silently halves the SEM data, GSE252378's 27 KMT2A-fusion samples are 24 independent patients: three pairs are one patient sampled twice, GSM8006584 names its antibody KMT2A-C1 in its title, its characteristics field and its own filename, and KMT2A-C2 in its description - so keying the antibody off the free-text description gives patient TB-92-0488 two C2 libraries and no C1, H3K4me3 is by far the most reproducible track in primary infant leukaemia CUT&Tag - replicate rho 0.97-0.98 - which makes it both the assay's proof of competence and the benchmark that every fusion-site enrichment should be quoted against, HOXA is occupied as a 107 kb cluster; IRX1 is occupied as one gene, with both IRX clusters cold, HOXA occupancy is the partner-invariant: occupied in 17 of 18 non-AFF1 KMT2A-r samples, 2.94x to 29.1x, HOXA9/HOXA10 is unoccupied and unmethylated at H3K4 in two of the three primary infant KMT2A::AFF1 states, while the SEM cell line carries the strongest AFF1 signal over that locus of any sample in the deposit, HOXB4, the one direct IRX1 target with ChIP evidence, carries no oncoprotein in any of seven infant patients, iALL-HOXA9 — the HOXA-high state of infant KMT2A::AFF1 ALL, and the one everything is modelled on, iALL-IRX1 — the HOXA-negative, IRX1-high state of infant KMT2A::AFF1 ALL, If the target promoter set is no more conserved within a patient than between patients, then nothing in the oncoprotein complex remembers the first disease, In 18 of 27 patient samples, comparing two antibodies raised against the SAME end of KMT2A calls at least as many oncoprotein-target promoters as the real N-over-C comparison does, and swapping the antibody pair moves a sample's own call count by a median of 2.57x, In the HOXA-dead infant states IRX1 carries H3K4me3 and ENL while HOXA9/HOXA10 carry neither, Independent positive control: of 27 samples, the ONE that calls zero oncoprotein-target promoters is 152985 - the AML that arose during menin-inhibitor treatment, which the paper reports as having oncoprotein and menin reduced to undetectable levels, IRX1 — Iroquois homeobox 1, the gene that names the HOXA-negative half of infant t(4;11) ALL, IRX1 binds the MLL-AF4 complex non-competitively — menin, LEDGF and DOT1L are all unchanged, IRX1 carries the KMT2A::AFF1 oncoprotein in exactly the patients where HOXA does not — seven patients, GSE252378, IRX1 CUT&RUN in primary t(4;11) blasts — testing Kühn's HEK293T mechanism where it matters, IRX1 fusion occupancy is confined to KMT2A::AFF1: 0 of 18 samples across five other partners, IRX1 is a second address for the KMT2A::AFF1 oncoprotein, not merely the gene that turns HOXA off, IRX1 occupancy is a lineage-switch cell state, and in GSE252378 it is confounded with the AFF1 partner and one institution, IRX1 occupancy under PARTIAL menin inhibition in KMT2A::AFF1, with a spike-in, because complete eviction destroys the readout, IRX2 is not fusion-occupied at promoter scale in GSE252378: 0 of 27 samples, against a null of 2.73, KMT2A-N CUT&RUN in an untreated non-AFF1 lineage-switching blast: the one experiment that separates partner from cell state, Measure IRX1 transcript and KMT2A-N oncoprotein occupancy in the SAME KMT2A::EPS15 blast - the one cell where expression-without-occupancy is most likely and has never been paired, Menin CUT&RUN in an IRX1-high KMT2A::AFF1 blast — the missing track in every public deposit, On one universe with one rule and a structure-respecting null, the two lineages of one infant overlap no more than two unrelated KMT2A::AFF1 infants do, p279 and p318: one infant, two diseases, and an oncoprotein target map that does not carry over, p279 carries the oncoprotein at HOXA AND at IRX1 — the published mutual exclusivity is not mutual exclusivity at chromatin, Paired IRX1 RNA and KMT2A-N occupancy in the same non-AFF1 blasts: does the expression subgroup exist where the occupancy subgroup does not?, Partner-protein occupancy is not fusion occupancy: every KMT2A::AFF1 chromatin claim resting on an AFF1, AFF4 or SEC-subunit ChIP is an upper bound that includes free complex, Picking a GEO supplementary file by slot number instead of extension substitutes a depth-normalised bigWig for a raw fragment BED in 107 of this deposit's 171 records, Pooling the two AF4 antibodies, as the published analysis does, drops AFF1's fusion-site enrichment from 1.8-4.6x the null to 0.8-2.1x - below the H3K4me3 negative control in all three samples, POST HOC: against institution-matched, anchored comparators the same-patient pair has the LOWEST excess in all six factorial cells - which leans to q142, but was not pre-registered, PROM1 (CD133) occupancy tracks HOXA occupancy at Spearman +0.952 — a second, independent marker of the same split, PROM1 occupancy tracks HOXA at +0.93 in KMT2A::AFF1 and not at all elsewhere; it is near-absent in KMT2A-AF9 and -AFDN despite high HOXA, q142's exact comparison - p279 against its own switched AML versus p279 against an unrelated infant - replicates in q144's own universe with q144's own rule, and q144 never made it, q145's anti-correlation p = 0.0288 is a one-sided value; the two-sided exact p is 0.0576 and the rho reproduces exactly, Run a fusion-specific and a total-AFF1 readout side by side in the same KMT2A::AFF1 nuclei, and report the two target sets rather than one, Scored in the published criterion's own currency, the number of oncoprotein-target promoters runs 0 to 2282 across 27 KMT2A-rearranged patient samples - 20.01x between the 10th and 90th percentiles - and the spread widens to 61.10x after depth matching, SEM, the standard t(4;11) model line, has zero signal at IRX1 — every model of this disease is a model of one subgroup, Single-cell CUT&Tag on p279 — is the double-positive blast one cell state or two clones?, Swap the AFF1 C-terminus onto a KMT2A-AF9 backbone and score IRX1 occupancy: the direct test of partner causality, The '0.400, keeps 1,894 of 2,045 calls' in the dispatch brief is two independent per-sample call counts read as a retention ratio; the intersection is 1,116 of a 2,812 union, The 'raw library promoter mean' that two cycles treated as library coverage tracks the in-promoter fragment FRACTION at Spearman +0.993 and true sequencing depth at only +0.292, and the oncoprotein share correlates with true depth at -0.255, The 0.069 chance floor quoted beside the 0.400 same-patient Jaccard is the cohort MEDIAN's null, and this pair's own floor is 0.267, The B-ALL and the AML of one infant share no more fusion-occupied promoters than two unrelated infants do - lineage, not patient identity, sets where KMT2A::AFF1 sits, The CD34+ oncoprotein-negative sample that calibrates the published N/C threshold is in GSE159608, not GSE252378 - so the 1.75 threshold cannot be re-derived from the deposit that carries the 27 patients it is applied to, The coverage guard withheld 30 of 351 pairs and named every one: 26 contain 152985, which calls zero promoters, and a Jaccard with a zero-call sample is a division, not a measurement, The deposit's two lineage-switching patients behave in opposite directions: the untreated pair keeps 1126 of its 2045 oncoprotein-target promoters across the switch, while the menin-inhibited pair falls from 345 to zero - so lineage switching does not by itself clear the oncoprotein, The dispatch brief scoped this deposit's oncoprotein-score arm at two patients and a cell line; it is 27 patient samples across six fusion partners, and the scoping error was inherited from a beat that only needed three of them, The EGR1 promoter fails its own IgG control — an attractive claim withheld because a pre-declared control said no, The excess overlap survives a structure-respecting null in both beats - permutation p = 0.0005 in all six cells - but every published excess figure shrinks 2.4- to 4-fold, The fusion-specific score's per-promoter reliability inside one patient is r = 0.183, and the median correlation between two DIFFERENT patients is 0.196 - so the ordering question cannot be resolved at promoter resolution, and the corpus's 0.82-0.97 figures cannot be carried to this readout, The GMP-like peak class is fusion-enriched in exactly one of GSE252378's 27 KMT2A-rearranged samples - p318, the sample it was derived from - once the null is matched on how coverable those promoters generically are, The HOXA-negative, IRX1-negative KMT2A-rearranged blast, The HOXA/IRX1 anti-correlation does not reproduce in KMT2A-ENL, the only other partner group that can carry one, The infant menin-inhibitor occupancy experiment has been done and deposited - menin, KMT2A and ENL CUT&RUN under revumenib in ONE infant patient sampled before and after a lineage switch, not two patients - but it is KMT2A-ENL, so the index-fusion absence survives, and the same deposit holds untreated KMT2A::AFF1 libraries this corpus cites once, The IRX1 address requires the AFF1 partner; the menin interface explains the shared HOXA address and not this one, The KMT2A::AFF1 oncoprotein-target promoter set is a fusion-level property, and patient identity adds nothing measurable on top of it, The lineage-switched AML state of infant KMT2A::AFF1, described by chromatin rather than by flow cytometry - fusion retained on PAX5 and MEIS1, lost from EBF1 and HOXA, myeloid promoters gained by DOT1L and ENL, The menin interface cannot be what decides where KMT2A::AFF1 sits: within one patient the fusion's target promoters were almost entirely replaced while the menin-binding motif was unchanged, The menin interface is identical in all 27 of these patients and the amount of chromatin their oncoproteins occupy differs by up to two orders of magnitude - so the interface can be a permission for binding but cannot be what sets how much binding happens, The oncoprotein-target site count for sample 148752 is 46, 345 or 745 depending on the interval set and the universe, and the corpus has been quoting one of the three with no label, The pre-registered magnitude test failed because the statistic was bounded by construction - top-decile share spreads only 1.1-1.4x between samples and cannot express what the published oncoprotein score says varies, The score's amplitude correlates with sequencing depth at Spearman -0.474 (p = 0.012) - a real and significant depth dependence that cleared the pre-registered voiding threshold of 0.6 only because the threshold was set loosely, The taspase-1 N/C antibody control separates fusion-occupied from wild-type KMT2A promoters in every primary infant sample, and it is the C-terminal arm that does the work while being the less reproducible arm, The unbounded oncoprotein score spans 1.73-12.32 log2 units within a sample - it is not the compressed statistic q142 was stuck with - and the pre-registered magnitude verdict is STILL void, because the score's amplitude is no larger than the disagreement between two antibodies against the same end of KMT2A, Three of eight CUT&RUN libraries are too shallow for a zero to mean anything — measured, not assumed, Two KMT2A-rearranged patients share oncoprotein-target promoters at a median Jaccard of 0.132 against an independence expectation of 0.069 - an enrichment of only 1.63x, with 5 of 351 pairs at or below chance, Two of ten hand-typed genomic intervals in this beat were on the wrong chromosome or a megabase off, and neither produced an error - one would have published the exact opposite of the truth about PAX5, Two of three KMT2A::EPS15 infant ALL cases carry IRX1 at KMT2A::AFF1 magnitude, while the only KMT2A::EPS15 patient with occupancy data has no oncoprotein at IRX1 at all, Under revumenib the oncoprotein leaves chromatin globally, so 'does IRX1 become a menin-inhibitor escape route' cannot be answered from this deposit, When one infant's KMT2A::AFF1 B-ALL became an AML, EBF1 lost fusion occupancy and PAX5 kept it - the B-lineage transcription-factor programme is not vacated as a block
350. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 39121437
     Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101).

     Issa GC, Aldoss I, Thirman MJ, DiPersio J, Arellano M, Blachly JS, et al., Stein EM · J Clin Oncol 43:75-84 2024
     used by A documented absence: not one endocrine outcome measure across the three lead menin-inhibitor trials, Analysis (runnable): value a menin inhibitor as a short-duration instrument — cohort meta-regression plus a discrete-event model of remission months, AUGMENT-101 (NCT04065399) — the registration trial, and what 22.8% actually means, AUGMENT-101: the partner composition of the trial that approved a menin inhibitor, with KMT2A::AFF1 at n=2 evaluable, Bounded absence: no menin-inhibitor trial reports response rate by 3-prime fusion partner in the primary literature, Duration and reinvestment risk — a 4.6-month response is a short-duration instrument, and short duration changes everything about how you value it, Experiment: measure the two missing time constants — how fast the KMT2A::AFF1 program collapses on drug, and how fast it comes back off drug, Flow-cytometric MRD: the fastest readout, and the one a lineage switch walks straight out of, Hypothesis: a defined subset of fusion binding sites survives saturating menin inhibition on menin-independent tethering, and that residual set is where bypass resistance comes from, Hypothesis: menin-inhibitor effect is hysteretic — the program collapses faster than it recovers — so intermittent dosing can hold efficacy at much lower cumulative exposure, Hypothesis: prior therapy itself installs menin-inhibitor resistance, and the dose of prior therapy predicts it better than any mutation does, Hypothesis: the survival benefit of menin inhibition is governed by the rate at which it delivers patients to a curative consolidation, not by its remission rate — and the field is measuring the wrong thing, Intact PTH rises in 34% of patients on revumenib, and hyperparathyroidism is on the label, KMT2A-rearranged acute lymphoblastic leukaemia, KMT2A::AFDN (MLL-AF6), t(6;11)(q27;q23), KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23), KMT2A::ELL (MLL-ELL), t(11;19)(q23;p13.1), KMT2A::MLLT1 (MLL-ENL), t(11;19)(q23;p13.3), KMT2A::MLLT10 (MLL-AF10), t(10;11)(p12;q23), KMT2A::MLLT3 (MLL-AF9), t(9;11)(p21.3;q23.3), Menin dependence of a non-elongation KMT2A fusion has never been demonstrated — the counted absence, and what the pivotal trial actually enrolled, Menin dependence of KMT2A::MLLT3: the fusion the co-IP was done on, the largest named partner in the pivotal trial, and still no published response rate, Model: predicting who responds to a menin inhibitor - no patient-level data is public, so this cannot be trained either, MRD as a trial endpoint in KMT2A-rearranged leukaemia: high negativity rates, and almost none of them say which assay, Necessary is not explanatory: four different questions that a knockout answers as if they were one, Revumenib (SNDX-5613, Revuforj) — first approved menin–KMT2A interface inhibitor, Score the HSPC-like fraction on paired pre-treatment and on-treatment samples from KMT2A-rearranged patients receiving a menin inhibitor — a flow-first design with a single-cell confirmatory arm, Syndax Pharmaceuticals — revumenib (SNDX-5613), the only menin inhibitor licensed down to infancy, Systematic enumeration of menin-inhibitor resistance mechanisms: seven entries written, thirteen candidates rejected with reasons, t(11;19) is the largest named partner group in the revumenib registration trial - and the trial never resolves whether those patients have MLLT1 or ELL, The clinical outcome data do not support a single KMT2A class, and they do not refute the menin interface either, The KMT2A-fusion causal chain: six links, one measured ordering, and two arms that are parallel rather than sequential, The reversibility question: months of partial occupancy against a syndrome built from decades of loss, What MRD-negative actually means: a quantitative range, a laboratory judgement, and three incompatible definitions, What this beat searched, read and set aside - including one cell line the accession database has not caught up with, and one query that returns a clean zero
351. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     MLL_oncoprotein_levels_NatComms - processed data tables and the figure-generation notebook for Janssens et al. 2024

     Janssens DH · GitHub / Zenodo (the paper's Code Availability statement) 2024
     used by A filter-free promoter ranking with no peak caller and no target list recovers 40 of the top 50 published oncoprotein-target genes in the drug-free infant sample, and 0 of 50 in the drug-exposed one, ENL redistributes rather than persists: it is the only channel that holds more of its signal at the myeloid-program peaks than at the B-lineage ones, by 2.06x in my instrument and 1.26x in the authors' own - and in absolute terms it falls further than menin does, Spike-in-normalised paired KMT2A N- and C-terminal CUT&RUN, with a fusion-junction readout, in a HOXA-negative KMT2A-rearranged blast beside a HOXA-positive one from the same institution and batch, The authors' own deposited table puts menin at 0.87 of its diagnostic-sample signal over their oncoprotein-target peaks, in the sample their text describes as having menin reduced to undetectable levels - the two statements are about different denominators, and only one of them travels, The compound in the only infant menin-inhibitor occupancy sample is revumenib, named in the abstract - and neither the dose nor the duration of exposure is recorded in the paper, the GEO record or the authors' repository
352. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetPMID 38212634
     A new genomic framework to categorize pediatric acute myeloid leukemia

     Umeda M, Ma J, Westover T, et al. · Nat Genet 56:281-293 2024
     used by A fusion-versus-rest expression difference can be pure morphology composition - I published one at p below 1e-12 and it dissolved inside every FAB stratum, aml_stjude_2024 - 887 paediatric AML cases with per-sample KMT2A fusion-partner structural-variant calls for all 180 KMT2A-rearranged cases, plus mRNA-seq and FAB morphology, GSE252378 contains no megakaryoblastic sample, so the 0-of-18 non-AFF1 IRX1 occupancy bound does not cover the one subgroup where IRX1 is actually expressed, IRX1 expression in KMT2A-rearranged paediatric AML is a FAB-M7 megakaryoblastic property, not a fusion property: 13 of 20 M7 versus 2 of 96 M5, and non-KMT2A-r M7 is 54 of 97, IRX1 status is set by the cell of origin, and the fusion partner predicts it only because different partners transform different cells - so the partner supplies no IRX1 address, The HOXA/IRX1 mutual exclusivity is reproduced at the transcript level in 48 KMT2A::AFF1 infant ALL cases (Fisher two-sided p < 1e-6) and is ABSENT in KMT2A::MLLT1 and in KMT2A-germline controls
353. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 38374003
     Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins.

     Chen TQ, Huang HJ, Zhu SX, et al. · Exp Hematol Oncol 2024
     used by A long non-coding RNA binds DOT1L's catalytic domain and turns its activity up - and blocking it makes the fusion protein itself get eaten, DOT1L's localization record is a mouse kidney paper wearing a human label - and the one image of it in a leukaemia cell is a supporting figure a title search cannot see, The lncRNA-DOT1L-LAMP5 axis was measured on H3K79 in MOLM-13 alone: eight human samples, one fusion, no index-fusion arm
354. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 38954782
     Open-Label, Multicenter, Phase I/II, First-in-Human Trial of TK216: A First-Generation EWS::FLI1 Fusion Protein Antagonist in Ewing Sarcoma.

     Meyers PA, Federman N, Daw N, Anderson PM, Davis LE, Kim A, Macy ME, Pietrofeso A, Ratan R, Riedel RF, Trucco M, Breitmeyer JB, Toretsky JA, Ludwig JA · J Clin Oncol 2024
     used by A pocketless fusion already had its protein-protein-interface drug taken to phase I/II - and TK216 turned out to be a microtubule destabiliser, not an EWS::FLI1 antagonist. This is the closest thing the field has to a controlled failure of the interface hypothesis.
355. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39649118
     Alternative splicing generates isoform diversity in MEN1.

     Ramachandran A, Le Quesne Stabej P, Boyle V, Elston MS, Pattison S, Lawrence B, et al. · Endocrine Oncology 2024
     used by A residue axis for menin, derived from coordinates: three spatial lobes, not four named ones, and the sharpest seam in the protein runs through the drug pocket
356. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39717192
     Case Report: A case of infantile acute hyperleukocytic leukemia treated by leukapheresis.

     Bian S, Li N, Gao H · Frontiers in Pediatrics 2024
     used by A six-month-old with a week of coughing: KMT2A::AFF1 pro-B ALL presenting with extreme hyperleukocytosis
357. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38750015
     Post-translational modification-dependent oligomerization switch in regulation of global transcription and DNA damage repair during genotoxic stress.

     Talukdar P, Pal S, Biswas D · Nature Communications 15(1):4128 2024
     used by Acetylation is a cycle, not a mark - and this graph holds one complete cycle, on a residue the fusion throws away, ATM - the DNA-damage kinase that phosphorylates three of the four KMT2A 3' partners, DNA-PKcs phosphorylates AF9 at S395 and releases it from the super elongation complex - the only AF9 regulatory element the fusion keeps, Four regulatory elements on AF9, and the fusion keeps exactly one - the phospho-switch that controls SEC binding, HDAC5 - the eraser in an existing entry's own id, and the one HDAC in this graph that erases a mark on a fusion partner protein rather than on a histone, Immunoprecipitate the KMT2A fusion and map its phosphosites - the experiment this whole field has never done, Induction chemotherapy phospho-inactivates KMT2A fusions through PIKK sites the partner retains - and a DNA-PK or ATM inhibitor would block that, KAT2B / PCAF - named in an existing entry's own id and never written, and the only acetyltransferase in this graph whose substrate is a fusion partner protein, Knock S395A into the MLLT3 half of a KMT2A::MLLT3 model and ask whether it becomes chemotherapy-resistant, PRKDC / DNA-PKcs - the kinase that phosphorylates AF9 on the one regulatory residue the fusion keeps, Q25 enumeration: what was searched, found, rejected and could not be read across the five 3' partners, The AF9 acetylation arm: PCAF at K339, HDAC5 gated by CaMKII - a kinase-controlled switch the fusion throws away
358. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38892207
     Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia

     Adriaanse FRS, Schneider P, Arentsen-Peters STCJM, et al. · International Journal of Molecular Sciences 2024
     used by Adaptive, non-genetic resistance — the leukemia keeps the fusion and rewires how it is maintained, Cell state in KMT2A-rearranged leukaemia is organised by lineage, not by the fusion — five independent axes split the same way, and every one of them splits AML from ALL rather than partner from partner, Dynamic BH3 profiling before and after menin inhibition — a one-week assay on primary cells that would choose the BH3-mimetic partner, and has never been run in lymphoid disease, Experiment: does chemotherapy itself install menin-inhibitor resistance? The two-arm controlled test, plus the serial-sample ladder, Experiment: time-to-resistance, not synergy index, as the readout for menin-inhibitor combinations, H3K79 methylation is what keeps Polycomb off - and that, not gene silencing, is what a DOT1L inhibitor actually undoes, Hypothesis: genetic and non-genetic escape from menin inhibition are substitutes, so MEN1 mutations will be rare in infants and the field's resistance biomarker will fail in children, KMT2A-rearranged acute lymphoblastic leukaemia, Pinometostat (EPZ-5676) — the DOT1L inhibitor, and the most instructive failure in this field, The menin-inhibitor-resistant state has its own address: SMARCA4, BRD4 and CREBBP, with no MEN1 mutation anywhere, The state under menin inhibition — differentiation in AML, rapid death in ALL, and a GMP-like exit in the cells that switch lineage instead, Venetoclax in KMT2A-rearranged leukemia — the apoptotic partner every other drug needs
359. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 39251607
     Systematic identification of post-transcriptional regulatory modules.

     Khoroshkin M, et al. · Nat Commun 2024
     used by AFF1's modern proximity neighbourhood is four RNA-binding proteins - NPM1, RBM15, SBDS, ZRANB2 - and it barely overlaps AFF4's, AGGF1 - an angiogenic G-patch protein whose BioID neighbourhood contains ELL, KMT2A, LEDGF, WDR5, KAT7 and RNA polymerase II, BUD13 - a RES-complex splicing factor 1.66 Mb from KMT2A on 11q23.3, whose one chromatin paper puts it in the soluble fraction, DDX55 - a large-subunit rRNA helicase that is nucleolar by imaging and nucleoplasmic by its own founding paper, and the narrowest RBP bait to reach KMT2A after DDX52, HNRNPC - the nascent-RNA packaging protein whose BioID neighbourhood contains AFF4, ELL, ENL, CDK9, cyclin T1 and KMT2A, ILF3 / NF90 - a nucleolar dsRNA-binding coactivator whose chromatin residency was mapped in the same leukaemia line that proximity-labelled KMT2A, LIN28B - a one-row BioID prey of KMT2A that a 2026 Blood paper shows is REQUIRED for KMT2A::AFF1 to transform human fetal cells, Menin's 33 curated partners, enumerated: 10 written, 10 discarded as mutation-directed or single-method, 3 that are not proteins, and what was read and rejected, Nobody has ever run proximity labelling on a KMT2A fusion, and the interaction records that look like they did are RBP-atlas preys from HEK293, Prey recovery in the two BioID depositions tracks SIZE and not abundance - and the interactome tail was being scored on the wrong side of the pair, because every one of the 22 partners is the BAIT and every core protein is the PREY, PSIP1-FASTKD2 declined: the bait is a mitochondrial matrix and nucleoid protein with two experimental localisations, the prey is nucleoplasmic LEDGF, and the row is one spoke-expanded BioID2 proximity in K562, PSIP1-UTP3 is one spoke-expanded BioID2 proximity row in K562 with UTP3 as bait and PSIP1 as prey at miscore 0.27; PSIP1 is recovered by 9 of the 50 baits in that screen and only 2 of the 9 are nucleolar, which is the panel's own base rate - declined, QKI - a KMT2A proximity row in K562, and a tumour suppressor whose loss concentrates in the HOXA subtype of T-ALL, Re-adjudicating the standing weak spot: proximity labelling HAS sampled AFF1, KMT2A and five leukaemia fusions - just never a KMT2A fusion, SMNDC1/SPF30 - a Tudor-domain splicing factor recovering ELL, ENL, KMT2A, PAF1 and KAT7, The 50-RBP BioID2 proximity map in K562 - the first modern proximity dataset this graph can reach, and AFF1 is in it as prey, The missing reagent: a KMT2A-fusion or wild-type-KMT2A proximity bait in a KMT2A-rearranged leukaemia line - IntAct has curated no KMT2A-bait interaction experiment since April 2015 and no PSIP1-bait since October 2012, U2AF1 - the 3' splice-site recognition factor, a speckle protein whose BioID neighbourhood contains LEDGF, ZC3H8 / Fliz1 - the last little-elongation-complex subunit without an entry, discovered in fetal liver haematopoietic progenitors, and a selective BioID2 bait that reaches KMT2A in K562
360. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 38554706
     The SPATA5-SPATA5L1 ATPase complex directs replisome proteostasis to ensure genome integrity.

     Krishnamoorthy V, et al. · Cell 2024
     used by AFG2A / SPATA5 (Q8NB90) - a 55LCC replisome-proteostasis ATPase that co-purifies with KMT2A and menin, and whose CURRENT symbol cannot retrieve its own source paper or any of its function literature, AFG2B / SPATA5L1 (Q9BVQ7) - the second 55LCC ATPase, the only read-queue member with an annotated nuclear pool, pan-essential in 95.5% of lines, and the one that touches PSIP1, Diffing the core scaffold's curated interactome against the graph: 46 of 217 partners are things here, CDK9 is not one of them, and the filter I built to rank the rest was counting one platform twice
361. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Agency (Wex legal encyclopedia)

     Legal Information Institute, Cornell Law School · Cornell Law School Legal Information Institute 2024
     used by Agency law — actual authority, apparent authority, and what revocation cannot undo
362. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 38011799
     Chaetocin-mediated SUV39H1 inhibition targets stemness and oncogenic networks of diffuse midline gliomas and synergizes with ONC201

     Xin D, Liao Y, et al. · Neuro-Oncology 2024
     used by All 39 bounded absences in this graph, classified by WHAT BOUNDS THEM: 23 rest on an abstract-level literature search, 7 on a threshold or a query filter, and only 2 on reading the primary source, An ENCODE-only archive bound systematically undercounts chromatin-modifying enzymes, because ENCODE's target catalogue is transcription-factor-shaped - measured 3-for-3 on the H3K9 machinery, with ratios of infinity, 2.8x and 7.3x, GSE225028: SUV39H1 and H3K9me3 CUT&RUN in SU-DIPG13 and SU-DIPG36 - the only published human SUV39H1 occupancy map deposited as a readable hg38 bigWig, and the enzyme and its own mark were profiled in the same cells, Read at last, against a pre-registered class-matched null: in SU-DIPG13 and SU-DIPG36 the SUV39H1 CUT&RUN mean at the KMT2A exon-11 CTCF anchor is 0.0000 and 1.6660 - the first an EXPLICIT zero record, not missing data - and no one of the seven KMT2A intervals in either line exceeds 1.21x the genome-wide random-tile mean. The pre-registered NEGATIVE prior held., The GEO sweep that q110 named as free and did not run: SUV39H1 chromatin occupancy HAS been measured in two human cell types, six samples, hg38 bigWigs already deposited - so the writer half of the H3K9me3 absence is measured-not-analysed, not never-measured
363. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39002676
     MLL-AF9 regulates transcriptional initiation in mixed lineage leukemic cells.

     Yang Z, Zhang G, Zhao R, et al. · J Biol Chem 2024
     used by An anti-MLL-N antibody sees the wild-type allele and the direct fusion, and nothing else - and cannot rank them, Anti-AF9 antibodies see three proteins, not two - and the third is an internal-promoter isoform discovered in 2025
364. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38682900
     Ribosome subunit attrition and activation of the p53-MDM4 axis dominate the response of MLL-rearranged cancer cells to WDR5 WIN site inhibition.

     Howard GC, Wang J, Rose KL, et al. · eLife 2024
     used by Analysis (planned) — comparative druggability scan of every obligate fusion-partner interface in the atlas, ASH2L — the WRAD subunit that has DPY30's essentiality profile and none of its co-dependency signal, BET bromodomain inhibition in KMT2A-rearranged leukemia — spectacular preclinically, stalled clinically, DPY30 — the smallest COMPASS subunit, and the only one that behaves like a selective dependency, Experiment (proposed) — cross-family interface point-mutant panel: is the obligate interface real in each fusion?, Four ways a WDR5 result can be true and have nothing to do with KMT2A, Hypothesis — the menin lesson generalises: every non-enzymatic fusion has an obligate partner interface that is more druggable than the fusion, Lost from the KMT2A half: the WIN motif and the whole WRAD interface (aa 3762-3767, Arg3765), RBBP5 — a WRAD subunit that binds the one part of KMT2A every fusion throws away, Verdict on the WRAD contradiction: the graph is right, its citation class is wrong, and its universal is wrong, WDR5 — the partner that is not a partner: it binds the half of KMT2A the fusion throws away, WDR5 and KMT2A are at the centrosome and the midbody - a non-chromatin address for both, with a patient-cell phenotype, WDR5: an established wild-type KMT2A contact, and no fusion contact ever measured
365. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 38678092
     The KMT2A/MLL consensus gene structure: a comprehensive update for research and diagnostic implications

     Meyer C, Larghero P, Lopes BA, Marschalek R · Leukemia 2024
     used by Analysis (runnable): does product viability leave a signature in the KMT2A breakpoint map once DNA fragility is controlled for?, Analysis (runnable): is anything actually enriched at KMT2A breakpoints? The test has never been run against a background that could say no, Breakpoint anatomy, and an audit of the prognosis claim, Each partner prefers a different KMT2A exon: partner-specific break position in 3,401 patients, KMT2A / MLL1 — the gene that breaks
366. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39039081
     Molecular insights into degron recognition by CRL5ASB7 ubiquitin ligase.

     Zhou J, Wang Y, et al. · Nature Communications 2024
     used by ASB7 (Q9H672) - the brake on H3K9me3's own positive feedback loop, released by CDK1 in mitosis, and it reached this graph as the flattest dependency in the read queue
367. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38498025
     The TLK-ASF1 histone chaperone pathway plays a critical role in IL-1beta-mediated AML progression.

     Lin HY, Mohammadhosseini M, McClatchy J, et al. · Blood 2024
     used by ASF1A - the compensating paralogue: the only gene in this beat that is not required in a single one of 1,208 cell lines, and it still has a leukaemia phenotype, ASF1B - the paralogue that actually does the work in blood: it occupies >70% of H3.3 nucleosomes in fetal liver while HIRA is dispensable there
368. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39479812
     [Chidamide Combined with (+) -JQ-1 to Kill MLL-Rearrangement Acute Myeloid Leukemia Cells by Disrupting the DNA Damage Response Pathway].

     Zhang Q, Li FM, Wang W, Zhang ZH, Zhang RJ, Ma MS, et al. · Zhongguo Shi Yan Xue Ye Xue Za Zhi 2024
     used by ATR - the replication-stress kinase with the best preclinical case in this disease and the best published reason not to inhibit it, CHEK1 (CHK1) - the node where this graph's chidamide synergy actually lands, and the reason that synergy is an HR-impairment argument, CHEK2 (CHK2) - named in every combination mechanism here and measured on its own in none of them, H2AX - filed as a gene and not as a mark, and the reason that decision changes what the graph can say, TP53BP1 (53BP1) - the end-protection factor that decides between the two repair routes, reachable only under the wrong symbol
369. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38867582
     Azacitidine as epigenetic priming for chemotherapy is safe and well-tolerated in infants with newly diagnosed KMT2A-rearranged acute lymphoblastic leukemia: Children's Oncology Group trial AALL15P1.

     Guest EM, Kairalla JA, Devidas M, et al. · Haematologica 2024
     used by Azacitidine - the one hypomethylating agent actually given to infants with KMT2A-rearranged ALL: safe, demonstrably demethylating, and it did not change survival, COG AALL15P1 — azacitidine epigenetic priming in infant KMT2A-rearranged ALL: on-target, well tolerated, no survival effect, Decitabine's target is a pan-essential gene, and KMT2A-rearranged lines depend on it LESS than other leukaemia lines - rank 16,949 of 17,728, The KMT2A-r DNA methylation signature — focal hypermethylation, no global hypomethylation, and a hypomethylating agent that did not help
370. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38437498
     BRG1/BRM inhibitor targets AML stem cells and exerts superior preclinical efficacy combined with BET or menin inhibitor.

     Fiskus W, Piel J, Collins M, Hentemann M, et al. · Blood 2024
     used by BAF does not work where the fusion works: most direct MLL-AF9 targets do not respond to Brg1 loss, and the SWI/SNF address is a distal MYC enhancer cluster 1.7 Mb away, BAF inhibition against the menin axis: on the evidence it is a complement, not an alternative - and the case rests on one laboratory, FHD-286 - the dual BRG1/BRM inhibitor that carries every SWI/SNF therapeutic claim in this disease, with a minimum enrolment age of 16, Is MYC the node? Two papers, the same MLL-AF9 model, opposite answers - and the second one failed to rescue, SMARCA2 (BRM) - the paralogue nobody measured, and the reason a DepMap rank cannot predict what a BRG1/BRM inhibitor does, SMARCA4 (BRG1) - a tumour suppressor by mutation and a maintenance requirement by knockdown, and in KMT2A-rearranged lines the dependency data say it is not selective at all, The menin-inhibitor-resistant state has its own address: SMARCA4, BRD4 and CREBBP, with no MEN1 mutation anywhere
371. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38452334
     Bahcc1 is critical for the aberrant epigenetic program in a mouse model of MLL-ENL-mediated leukemia

     Nakamura A, Masuya M, Shinmei M, Tawara I, Nosaka T, Ono R · Blood Adv 2024
     used by BAHCC1 - a BAH-domain H3K27me3 reader that an MLL fusion binds and upregulates in mouse, and the locus carrying the two largest MLL1-N-reactive rises under a menin inhibitor in human RS4;11
372. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38802066
     RUNX1::ETO and CBFbeta::MYH11 converge on aberrant activation of BCAT1 to confer a therapeutic vulnerability in core-binding factor-acute myeloid leukaemia.

     Wang S, Liu Y, Zhao X, ..., Wang K · Br J Haematol 2024
     used by BCAT1 in core-binding-factor AML - the closest analogue in another fusion family, where TWO different fusions converge on one metabolic enzyme by rewiring the chromatin at its locus
373. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38273654
     Base editing of key residues in the BCL11A-XL-specific zinc finger domains derepresses fetal globin expression

     · Molecular Therapy 2024
     used by BCL11A — the sickle-cell target whose binding sites lose methylation in this disease
374. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 38923173
     Acquired copy number amplification at the MYC enhancer in human B-precursor acute lymphoblastic leukemia cell lines.

     Watanabe A, Wang L, Tan TK, Urayama KY, Kizuki T, Komatsu C, et al. · Cancer Sci 2024
     used by BENC - the MYC blood enhancer cluster 1.7 Mb downstream, required for MLL-AF9 leukaemia maintenance, and named in zero entries of this graph until now, Is BENC even on in the disease this project is about? A module-resolved accessibility and deletion map in KMT2A::AFF1 B-lineage cells
375. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.news
     Menin inhibitors for AML: Current status and insights from ASH 2024 (bleximenib cAMeLot-1 dose optimisation data)

     AML Hub editorial team (reporting Jabbour E et al., ASH 2024) · AML Hub 2024
     used by Bleximenib (JNJ-75276617) — menin inhibitor with a cleaner cardiac profile, and the only one with a 2-year-old floor
376. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 38989615
     BOD1L mediates chromatin binding and non-canonical function of H3K4 methyltransferase SETD1A

     See PubMed record PMID 38989615 for the full author list (not transcribed here) · Nucleic Acids Research 2024
     used by BOD1L (BOD1L1) — the top SETD1A co-dependency, and the only candidate in this cycle tested by CRISPR tiling in a KMT2A::AFF1 line, No proximity, degron or tiling-CRISPR study has ever been run on WRAD in KMT2A-fusion leukaemia, RBBP5: the thinnest fusion literature of the four subunits, and one chromatin datum, SETD1A — a leukemia dependency whose enzyme activity turns out to be dispensable, Target safety triage v2: constraint with its uncertainty attached (run), The bite-back of striking a target: a wrong strike costs a cure and generates no data that it was wrong, The dependencies this project keeps failing to see are the buffered ones: paralogue redundancy and guide placement, not absence of biology, U4 was assumed, so I tested it: full text raises the low claim-to-paper overlap scores with a +0.108 median margin over same-field decoys (42% of the raw rise is document length), and every one of the seven pairs that stays low is a blind spot in my own instrument rather than a misattached citation
377. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 39362248
     Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): a multicentre, open-label, multi-cohort, phase 1 trial.

     Wang ES, Issa GC, et al. · Lancet Oncol 2024
     used by Bounded absence: no menin-inhibitor trial reports response rate by 3-prime fusion partner in the primary literature, Counted absence: no menin-inhibitor trial has ever reported a response RATE in NUP98-rearranged patients, Jolanta Grembecka & Tomasz Cierpicki (University of Michigan) — the chemistry that made the menin interface druggable, Kura Oncology — ziftomenib (KO-539): an adults-only sponsor that quietly supplies infant trials, Of 62 registered menin- or DOT1L-inhibitor trials, 7 have stopped and none gave a safety reason - four were company or supply decisions - yet the same drugs carry dose-limiting differentiation syndrome and QT prolongation that the registry never mentions, Ziftomenib (KO-539, Komzifti) — once-daily menin inhibitor approved in NPM1-mutant AML
378. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39099338
     Prenatal origin of NUTM1 gene rearrangement in infant B-cell precursor acute lymphoblastic leukaemia

     Bardini M, Fazio G, Abascal LC, et al. · British Journal of Haematology 2024
     used by BRD9::NUTM1, t(5;15)(p15.33;q14) - one fusion is enough to make infant B-ALL in a mouse, and it is the one that behaves best in a child, NUTM1-rearranged B-ALL - the KMT2A-wild-type arm of the same infant trials, with 4-year EFS of 100% against 36-37% next door
379. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     REVUFORJ (revumenib) tablets, for oral use - Full Prescribing Information

     Syndax Pharmaceuticals, Inc. / US Food and Drug Administration · Drugs@FDA label NDA 218944 (218944s000lbl.pdf) 2024
     used by Breakthrough therapy and accelerated approval: the menin field took the fast review and declined the shortcut, Revumenib (SNDX-5613, Revuforj) — first approved menin–KMT2A interface inhibitor, What a menin inhibitor costs: the list price, worked out for an infant
380. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     NDA 218944 Approval Letter, REVUFORJ (revumenib) tablets

     US Food and Drug Administration, Center for Drug Evaluation and Research · Drugs@FDA (218944Orig1s000ltr.pdf) 2024
     used by Breakthrough therapy and accelerated approval: the menin field took the fast review and declined the shortcut, FAERS shows no endocrine signal for either menin inhibitor - and proves it could not have, FDA already required this study: PMR 4730-1 names endocrine-related disorders due to chronic menin inhibition, Hypothesis: the paediatric gap is set by the population ratio, not by paediatric biology, The cheapest study that would settle this: nine assays and a hand radiograph, on children already being followed, The counter-argument: the menin field is an adult field, and the infant studies were withdrawn, The EU paediatric investigation plan: an obligation, not an incentive - and the deferral is the loophole, The reversibility question: months of partial occupancy against a syndrome built from decades of loss, The same pocket suppresses JUND: menin inhibition's unmeasured endocrine liability in infants, Turn menin off for a defined window, then back on: the missing experiment that would bound reversibility
381. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 38583175
     Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval

     Liu ITT, Kesselheim AS, Cliff ERS · JAMA 331(17):1471-1479 2024
     used by Breakthrough therapy and accelerated approval: the menin field took the fast review and declined the shortcut
382. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38634141
     Outcome of infants with acute lymphoblastic leukemia treated with the Chinese Children's Cancer Group Acute Lymphoblastic Leukemia 2015 study protocol.

     Leung AWK, Cai J, Wan Z, Qin J, Fang Y, Sun L, et al. · Haematologica 2024
     used by Bringing down a white count of half a million in a four-kilogram baby, CNS disease at diagnosis in infants: a real excess, measured by a procedure that partly creates it, Dying in induction: the place where infant protocols actually differ, Fever and fatigue: two of the five headline signs cannot be elicited from a baby, Hyperleukocytosis: why a very high white-cell count is a medical emergency, Hypothesis: the spread in infant presenting-feature frequencies is mostly measurement, not biology, Infant acute lymphoblastic leukaemia (ALL diagnosed under 1 year of age), KMT2A-rearranged acute myeloid leukaemia in children and infants, Leukaemia diagnosed in the first month of life: a different presentation and a different prognosis, The white cell count at diagnosis in infants, and why the reported medians disagree by fivefold, WBC 300, age 6 months, MRD 0.01%: three lines drawn by committees, not by biology, WBC 300: a stratification convenience, not a biological threshold - and the evidence says so four different ways, When infant leukaemia comes back, it comes back early and while treatment is still running, Which MRD timepoint drives which decision in infant ALL, and how good the evidence for each is
383. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     BUSULFAN injection, for intravenous use - US prescribing information (Structured Product Label, ANDA215102)

     Eugia US LLC · DailyMed / FDA Structured Product Labeling, openFDA drug label API 2024
     used by Busulfan - the alkylating agent that replaces radiation in infant conditioning, and whose labelled paediatric target range is below the range the modern trial data support, Sinusoidal obstruction syndrome after infant conditioning - an age signal, a regulatory exposure threshold, and a prophylaxis that failed its randomised trial
384. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38892227
     SMYD3 Controls Ciliogenesis by Regulating Distinct Centrosomal Proteins and Intraflagellar Transport Trafficking.

     Agborbesong E, Zhou JX, Zhang H et al · International Journal of Molecular Sciences 2024
     used by C2CD3 - the centriole-elongation regulator fused to KMT2A exon 8 in an MPNST, predicted OUT OF FRAME, and the partner whose RefSeq transcript is 390 residues shorter than UniProt's canonical, SMYD3 - a lysine methyltransferase with three claimed histone marks and one robust non-histone substrate, sitting on an HOXA9 feed-forward loop in MLL-AF9 AML and a fatty-acid-oxidation axis in CML stem cells, with zero interventional trials
385. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 39167622
     A Phase 1 First-in-Human Study of the MCL-1 Inhibitor AZD5991 in Patients with Relapsed/Refractory Hematologic Malignancies.

     Desai P, Lonial S, Cashen A, ..., Blachly JS · Clin Cancer Res 2024
     used by Cardiac troponin release on MCL-1 inhibition - reported for two structurally distinct compounds and described by one developer as a likely CLASS effect, which makes it an essential-function ceiling rather than a chemistry problem, MCL1 - named in 34 entries of this graph with no entry of its own until now; a mitochondrial survival protein high in infant KMT2A-rearranged ALL, druggable, and so far undruggable in patients
386. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39362994
     Selective inhibition of HDAC class IIA as therapeutic intervention for KMT2A-rearranged acute lymphoblastic leukemia.

     Verbeek TCAI, Vrenken KS, Arentsen-Peters STCJM, Castro PG, van de Ven M, van Tellingen O, et al. · Communications Biology 7(1):1257 2024
     used by Catalytic-dead versus degrader: a four-arm test that resolves the HDAC7 direction conflict and supplies the pharmacodynamic marker this drug class has never had, HDAC5 - the eraser in an existing entry's own id, and the one HDAC in this graph that erases a mark on a fusion partner protein rather than on a histone, HDAC7 - the eraser the index fusion silences, where the proposed therapy is to INDUCE the HDAC, and two 2024-2025 papers point in opposite directions, No HDAC-inhibitor result in this disease attributes to an HDAC enzyme - the only per-enzyme evidence is genetic, and it says the enzyme is not fusion-specific, The HDAC7 direction conflict is scaffold versus catalysis: removing the protein and blocking its catalysis are opposite interventions, because class IIa HDACs barely have any catalysis
387. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38468826
     NG2 Molecule Expression in Acute Lymphoblastic Leukemia B Cells: A Flow-Cytometric Marker for the Rapid Identification of KMT2A Gene Rearrangements.

     Bisegna ML, ..., De Propris MS · Mediterr J Hematol Infect Dis 2024
     used by CD22 (SIGLEC2) - the antigen that comes on BEFORE CD19, which makes it both the backup target and the pre-loaded escape route, CD34 - named in 132 entries of this graph and written in none, and it does not mean what the graph has been using it to mean, CD38 - the one marker that is BRIGHTER in KMT2A-rearranged B-ALL, an antigen-targeted therapy that has already produced lineage switch, and an enzyme rather than a receptor, CSPG4 / NG2 - the flow-cytometry surrogate for a broken KMT2A, and a direct target gene of the fusion that makes it, IL3RA / CD123 - not just a myeloid target: the quartile of CD123 expression that carries the KMT2A rearrangements is the quartile that dies, What an immunophenotype can and cannot tell you about a genotype - the arithmetic of a surrogate marker, worked on NG2
388. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38766795
     Application and prognostic relevance of CD34 detection in immunophenotyping of pediatric acute B lymphoblastic leukemia.

     Zha W, ..., Zhuo JJ · Eur Rev Med Pharmacol Sci 2024
     used by CD33 (SIGLEC3) - the aberrant myeloid antigen on a B-lineage blast, and the one antibody-drug-conjugate target with a positive randomised result in KMT2A-rearranged disease, CD34 - named in 132 entries of this graph and written in none, and it does not mean what the graph has been using it to mean
389. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 38215390
     CD371-positive pediatric B-cell acute lymphoblastic leukemia: propensity to lineage switch and slow early response to treatment.

     Buldini B, ..., Dworzak MN · Blood 2024
     used by CD33 (SIGLEC3) - the aberrant myeloid antigen on a B-lineage blast, and the one antibody-drug-conjugate target with a positive randomised result in KMT2A-rearranged disease, CLEC12A (CD371, CLL-1, MICL) - the leukaemic-stem-cell antigen whose therapeutic rationale rests on an absence, and which menin inhibition appears to induce, DUX4::IGH (IGH-DUX4), t(4;14)/ins(14;4) — D4Z4 repeat insertion into the IGH locus, Lineage drift - the partial state between B-ALL and AML, and the fact that nobody has published the ORDER in which markers change, The immunophenotype beat's own ledger: what was enumerated, what was written, what was dropped and why, and what could not be read, Which marker moves first? A re-analysis of flow files that already exist, to put an order on lineage switch
390. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39528457
     p14ARF forms meso-scale assemblies upon phase separation with NPM1.

     Gibbs E, et al. · Nat Commun 2024;15:9531 2024
     used by CDKN2A - one gene, two reviewed UniProt records with the same primary symbol, and a deletion that is three times rarer here than in the infant leukaemias next door
391. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.book
     Infant Leukemia (StatPearls)

     StatPearls Publishing · NCBI Bookshelf 2024
     used by Central nervous system involvement at diagnosis in KMT2A-rearranged infant leukaemia, Hepatosplenomegaly: the swollen abdomen that is often the first thing a parent notices, KMT2A-rearranged acute myeloid leukaemia in children and infants, Leukaemia cutis: the skin nodules that can be the first sign of infant leukaemia, Pallor and fatigue: the anaemia of a marrow taken over by leukaemia
392. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     World Population Prospects 2024: Summary of Results

     United Nations Department of Economic and Social Affairs, Population Division · United Nations 2024
     used by Childhood leukaemia worldwide, ages 0-14, How many infants worldwide, not just in the United States
393. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
     ClinicalTrials.gov registry records for NCT05761171 (AALL2121: A Phase 2 Study of SNDX-5613 in Combination With Chemotherapy for Patients With Relapsed or Refractory KMT2A-Rearranged Infant Leukemia) and NCT00557193 (AALL0631), retrieved via the ClinicalTrials.gov API v2

     Children's Oncology Group; National Cancer Institute · ClinicalTrials.gov 2024
     used by Children's Oncology Group — the trial network, the AALL protocol series and the biobank that no single lab can substitute, Who holds the data and samples we cannot generate ourselves — an access map
394. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38360863
     Enhanced Risk Stratification for Children and Young Adults with B-Cell Acute Lymphoblastic Leukemia: A Children's Oncology Group Report

     DelRocco NJ, Loh ML, Borowitz MJ, Gupta S, Rabin KR, Zweidler-McKay P, Maloney KW, Mattano LA, Larsen E, et al. · Leukemia 2024
     used by Children's Oncology Group — the trial network, the AALL protocol series and the biobank that no single lab can substitute
395. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 39143217
     Recognition and control of neutrophil extracellular trap formation by MICL.

     Malamud M, Whitehead L, McIntosh A, Colella F, Roelofs AJ, Kusakabe T, et al. · Nature 2024
     used by CLEC12A (CD371, CLL-1, MICL) - the leukaemic-stem-cell antigen whose therapeutic rationale rests on an absence, and which menin inhibition appears to induce, Hypothesis: CLEC12A is a cell-intrinsic dependency in KMT2A-rearranged leukaemia, not only a surface marker - and if so, antigen-negative escape is self-defeating, Risk: CLEC12A-directed therapy ablates normal granulocytes and disables an inhibitory brake on NET formation - the toxicity is mature-myeloid, not stem-cell
396. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38306602
     Structural variants involving MLLT10 fusion are associated with adverse outcomes in pediatric acute myeloid leukemia.

     Abla O, Ries RE, et al. · Blood Adv 2024
     used by COG AAML0531/1031 (n=2,080): MLLT10 fusions are adverse, and the 5-prime partner barely changes it, One karyotype band, two partner genes: why t(11;19) and t(10;11) can cancel a real partner effect, The lineage confound: partner predicts whether the leukaemia is myeloid or lymphoid before it predicts anything else, Which partner, in which patient: KMT2A partner frequencies across six age-lineage strata
397. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38655899
     Condensate-Promoting ENL Mutation Drives Tumorigenesis In Vivo Through Dynamic Regulation of Histone Modifications and Gene Expression

     Liu Y, Li Q, Song L, et al. (Wan L, senior author) · Cancer Discovery 14(8):1522-1546 2024
     used by Condensates in KMT2A-fusion leukemia — an honest verdict: not established for AFF1/AFF4/AF9, load-bearing only in ENL-mutant and NUP98 fusions, ENL's nuclear annotation has no citation at all, and every picture of ENL in a nucleus is of a mutant or a fusion, never the wild-type protein, Where KMT2A and its fusions sit inside the nucleus — SNL1/SNL2, nuclear speckles and the condensate question
398. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38693103
     The epigenetic regulators EP300/CREBBP represent promising therapeutic targets in MLL-rearranged acute myeloid leukemia.

     · Cell Death Discov 2024
     used by CREBBP (CBP) — binds the KMT2A transactivation domain, which no fusion keeps, H3K27ac - named in 40 entries with no entry of its own, and the strongest KMT2A::AFF1 measurement of it is invisible to every abstract search
399. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39682177
     Patient-Specific Circulating Tumor DNA for Monitoring Response to Menin Inhibitor Treatment in Preclinical Models of Infant Leukemia.

     Doculara L, Evans K, Gooding JJ, et al. · Cancers (Basel) 2024
     used by ctDNA MRD under a menin inhibitor: blood flow diverges from blood DNA, because the disease is in the spleen and marrow, The 'infant ALL' PDX panel with four KMT2A::AFF1 models — one of which the full text calls adult
400. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37496439
     DNAJC10 maintains survival and self-renewal of leukemia stem cells through PERK branch of the unfolded protein response.

     Li M, Wu X, Chen M, Hao S, et al. · Haematologica 2024
     used by EIF2AK3 / PERK (Q9NZJ5) - the kinase whose transcript is flat under both inhibitors, whose arm IS functionally required in MLL-AF9 leukaemia stem cells, and whose common name collides with phospho-ERK
401. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39454110
     Super-Enhancer-Driven IRF2BP2 is Activated by Master Transcription Factors and Sustains T-ALL Cell Growth and Survival.

     Yu J, Zhang Z, Chen Y, Wang J, Li G, Tao Y, et al. · Adv Sci (Weinh) 2024
     used by ELF1 - a direct transcriptional target of MLL fusion proteins and HOXA9 that is ALSO a BioID neighbour of KMT2A, and that is focally deleted in paediatric AML without a KMT2A rearrangement
402. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39582094
     Identification of a Nuclear Localization Signal (NLS) in Human Transcription Elongation Factor ELL2.

     Kohrt S, Baheerathan A, Prokscha J, Zwosta A, Sticht H, Thoma-Kress AK · Cell Biochem Funct 2024
     used by ELL2 — a SEC subunit that almost no cell needs, next to a paralogue almost every cell needs
403. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 38750017
     Cryo-EM structures of the human Elongator complex at work.

     Abbassi NE, Jaciuk M, et al. · Nat Commun 2024
     used by ELP1 (IKBKAP/IKAP) - the Elongator scaffold that was first named for the IKK complex, is a paediatric-cancer predisposition gene, and has an RNA Pol II contact in IntAct, ELP2 (STATIP1/StIP1) - the double beta-propeller of the Elongator core, whose informal name collides with a different human gene and whose STAT3 function is a by-similarity annotation, ELP3 - the catalytic subunit, the only Elongator protein with a real acetyltransferase domain, and the one whose loss in mouse blood causes marrow failure and then p53-mutant leukaemia, ELP5 (DERP6) - the bridge that joins ELP3 to ELP4, the most essential Elongator subunit in DepMap, and a gene whose cytoplasmic call rests on an overexpression experiment, ELP6 (TMEM103/C3orf75) - an Elongator subunit named after a membrane protein it is not, whose entire localisation record comes from a Drosophila paper its own symbol cannot retrieve
404. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.preprintPMID 38234854
     KMT2A oncoproteins induce epigenetic resistance to targeted therapies.

     Janssens DH, Duran M, Otto DJ, et al. · bioRxiv 2024
     used by ENL stays after the fusion leaves — an epigenetic lesion that outlives the protein that made it, Hypothesis: menin inhibition pushes cells toward the GMP-like state, and the GMP-like state is where menin inhibition works best — so a lineage switch on therapy should predict response, not failure, Lineage switch as a menin-inhibitor escape route — documented in a patient on revumenib, and invisible to every resistance-mutation screen
405. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37917159
     Genome editing-induced t(4;11) chromosomal translocations model B cell precursor acute lymphoblastic leukemias with KMT2A-AFF1 fusion

     Pan F, Sarno J, Jeong J, et al. (senior author Cleary ML) · Journal of Clinical Investigation 2024
     used by ETO2::GLIS2 rewires chromatin in stages and hijacks the osteogenic homeobox factor DLX3 as its first required step — a genome-edited human iPSC model that resolves leukaemia initiation into an ordered sequence
406. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39475509
     NUP98 fusion proteins and KMT2A-MENIN antagonize PRC1.1 to drive gene expression in AML

     Heikamp EB, et al. · Cell Reports 43(11):114901 2024
     used by Evicting the fusion is not enough: PRC1.1 has to arrive, and losing it causes menin-inhibitor resistance in vivo
407. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39433902
     PRC2-EZH1 contributes to circadian gene expression by orchestrating chromatin states and RNA polymerase II complex stability.

     Liu P; Nadeef S; Serag MF; Paytuví-Gallart A; Abadi M; Della Valle F; Radió S; Roda X; Dilmé Capó J; Adroub S; Hosny El Said N; Fallatah B; Celii M; Messa GM; Wang M; Li M; Tognini P; Aguilar-Arnal L; Habuchi S; Masri S; Sassone-Corsi P; Orlando V · EMBO J 2024
     used by EZH1 - the paralogue that makes the approved EZH2 drug the wrong drug for this disease
408. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38241700
     Targeting the Epigenetic Reader ENL Inhibits Super-Enhancer-Driven Oncogenic Transcription and Synergizes with BET Inhibition to Suppress Tumor Progression

     Chen Y, Ying Y, Ma W, Ma H, Shi L, Gao X, Jia M, Li M, Song X, Kong W, Chen W, Zheng X, Muluh TA, Wang X, Wang M, Shu XS · Cancer Research 84(8):1237-1251 2024
     used by FACT (SPT16-SSRP1) - the chromatin arm of transcription elongation, and a clean negative result for the KMT2A::AFF1 interactome, SUPT16H (SPT16) - the large FACT subunit: pan-essential, an anti-dependency in KMT2A-rearranged lines, and drugged in MLL-r leukaemia by a compound that works through p53
409. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38243088
     Ontogeny shapes the ability of ETV6::RUNX1 to enhance hematopoietic stem cell self-renewal and disrupt early lymphopoiesis.

     Eldeeb M, Konturek-Ciesla A, Zhang Q, Kharazi S, Tingvall-Gustafsson J, Ungerbäck J, Sigvardsson M, Bryder D · Leukemia 2024
     used by Fetal-restricted permissive factors across fusion families - the class has exactly ONE fully worked member, and for ETV6::RUNX1 the fetal advantage is real but no factor is named
410. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Conflict of interest (Wex legal encyclopedia)

     Legal Information Institute, Cornell Law School · Cornell Law School Legal Information Institute 2024
     used by Fiduciary conflict of interest — law does not remove a conflicted agent, it separates the mandates
411. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39329074
     Activating mutations remodel the chromatin accessibility landscape to drive distinct regulatory networks in KMT2A-rearranged acute leukemia.

     Zhang Q, Falqués-Costa T, Pilheden M, et al. · Hemasphere 2024
     used by FLT3 / CD135 — the strongest non-tether co-dependency, and a target the field may have written off on a badly executed trial
412. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38113271
     GPATCH4 regulates rRNA and snRNA 2'-O-methylation in both DHX15-dependent and DHX15-independent manners.

     Kanwal N, Krogh N, Memet I, Lemus-Diaz N, Thome CC, et al. · Nucleic Acids Res 2024
     used by GPATCH4 (Q5T3I0) - a nucleolar and Cajal-body helicase cofactor in the pan-MLL-fusion core, with no DHX15 and no G-patch relative beside it
413. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.journal-articlePMID 39461037
     Rational fragment-based design of compounds targeting the PWWP domain of the HRP family

     Vantieghem T, ..., Strelkov SV · European Journal of Medicinal Chemistry 2024
     used by HDGFL2 / HRP-2 - the second IBD protein, which binds KMT2A at the same site with the same affinity and does NOT need menin to do it, LEDGF PWWP chemistry exists after all - 68 fragment hits, double-digit micromolar leads - and the pocket has a structural ceiling the NSD PWWPs do not, The paralogue that covers for LEDGF: HRP-2 carries the only other IBD in the human proteome, substitutes for LEDGF in HIV integration, and the double knockout is embryonic lethal
414. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39015025
     RGS1 and CREB5 are direct and common transcriptional targets of ZNF384-fusion proteins.

     Yamada C, Okada K, Odaira K, Tokoro M, Iwamoto E, Sanada M, Noura M, Okamoto S, Yasuda T, Tsuzuki S, Kiyoi H, Hayakawa F · Cancer Med 2024
     used by How common is ZNF384-rearranged leukaemia? Published answers span 1.6% to about 20% and the spread is almost entirely denominator, not biology
415. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38971327
     Clinicopathologic features and outcomes of acute leukemia harboring PICALM::MLLT10 fusion.

     Wang J, et al. · Hum Pathol 2024
     used by How common PICALM::MLLT10 is, and in which disease - 65% T-ALL, 27% AML, and invisible to karyotype half the time, Outcome in PICALM::MLLT10: children with ALL do reasonably well, children with AML do badly, and transplant does not rescue them, PICALM::MLLT10 (CALM-AF10), t(10;11)(p13;q14) - the DOT1L-dependent HOXA fusion that contains no KMT2A, The cell CALM-AF10 arrests: an early T-precursor in adults and a TCR-positive thymocyte in children - two states, split by age (corrected 2026-09-21)
416. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 38650127
     Importin 7 enhances protective autophagy induced by nuclear translocation of homeobox A10 in oral squamous cell carcinoma.

     Chen S, Pan J · Cell Mol Biol (Noisy-le-grand) 2024
     used by HOXA10 - named in 27 entries as part of the HOXA output and never written; a posterior HOX paralogue that is regulated with HOXA9 and tested far less often
417. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Severability clause (Wex legal encyclopedia)

     Legal Information Institute, Cornell Law School · Cornell Law School Legal Information Institute 2024
     used by Hypothesis: the KMT2A breakpoint map is shaped by product viability, not only by DNA fragility, and the signature is that breaks respect inter-domain linkers, Hypothesis: the reciprocal AFF1::KMT2A product protects only when it is structurally complete, so its prognostic effect is a breakpoint class in disguise, Severability (contract law) — what survives when a clause is struck, and what survives a KMT2A break
418. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38650597
     Proximally biased V(D)J recombination in the clonal evolution of IGH alleles in KMT2A::AFF1 BCP-ALL of all age classes.

     Müller H, Dicker F, Bär C, et al. · Hemasphere 2024
     used by Ig-based MRD fails specifically in the KMT2A-rearranged patients whose IGH repertoire is proximally biased and still recombining, MRD by Ig/TCR rearrangement: the standard in ALL, and the assay infant KMT2A-rearranged disease strains hardest, Programmed DNA breaks - V(D)J and class switching - and the verdict on whether either one breaks KMT2A, Proximally biased V(D)J and IGHV6-1 in KMT2A::AFF1: the Ig MRD target is a moving target, and the clinic had already moved, Retrospective paired-target MRD on stored Interfant marrows, stratified by IGHV usage
419. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38048400
     Targeting IGF2BP3 enhances antileukemic effects of menin-MLL inhibition in MLL-AF4 leukemia

     · Blood Advances 2024
     used by IGF2BP3 — an RNA-binding protein required for MLL-Af4 leukaemogenesis in mice that CRISPR barely touches in human lines, PTBP1 — the strongest RNA-layer dependency in KMT2A-rearranged lines, found by a domain-focused screen and missed by this beat's own gene panel, The decisive experiment: acute degron removal of IGF2BP3, IGF2BP2 and both, read on self-renewal and xenograft initiation rather than bulk dropout, The RNA layer and the menin interface are separable: IGF2BP3 depletion sensitises MLL-AF4 leukaemia to menin inhibition and outperformed it alone
420. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39532854
     Nuclear IMPDH2 controls the DNA damage response by modulating PARP1 activity.

     Espinar L; Garcia-Cao M; Schmidt A; Kourtis S; Gañez Zapater A; Aranda-Vallejo C; Ghose R; Garcia-Lopez L; Sheraj I; Pardo-Lorente N; Bantulà M; Pascual-Reguant L; Darai E; Guirola M; Montero J; Sdelci S · Nat Commun 2024
     used by IMPDH2 - the rate-limiting guanine-nucleotide enzyme whose inhibition lowers LEDGF and menin protein and dismantles the MLL-fusion complex itself
421. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39276940
     Drug-resistant menin variants retain high binding affinity and interactions with MLL1

     Ray J, Clegg B, Grembecka J, Cierpicki T · J Biol Chem 2024
     used by In a competitive menin-binding scaffold with assumed rates, the drug exposure needed scales with menin relative to the fusion-menin Kd, and whether recovery after a lapse lags collapse is governed by the drug's residence time - a conditional counter-lead to the pulsed-dosing premise, not a prediction, The ten reported menin-inhibitor escape substitutions are each one nucleotide change from the MEN1 sequence - which the sources could not have shown otherwise - so the useful outputs are a 25-variant validation panel and a burden threshold, not the headline
422. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38621200
     Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia.

     van Weelderen RE, Harrison CJ, Klein K, Jiang Y, et al. · Blood Adv 2024
     used by In childhood t(11;19), every lymphoblastic case was MLLT1 and every ELL case was myeloid - the one rule that lets an old cohort be de-contaminated, Spliced and balanced KMT2A::MLLT1 do not automatically make the same oncoprotein - unless you restrict the comparison, which nobody has, t(11;19) is the largest named partner group in the revumenib registration trial - and the trial never resolves whether those patients have MLLT1 or ELL, The partner-matched control arm is not 241 versus 219 - it is 153 versus 101, and in that subset the two groups make an identical fusion protein, Which partner, in which patient: KMT2A partner frequencies across six age-lineage strata, Who the 460 KMT2A::MLLT1 patients actually are: 88% lymphoblastic, 53% infants, and only 47 cases of AML in the whole series
423. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38890447
     Combination of menin and kinase inhibitors as an effective treatment for leukemia with NUP98 translocations

     Miao H, et al. · Leukemia 38(8):1674-1687 2024
     used by In NUP98-rearranged leukaemia, who responds to a menin inhibitor is decided by the co-mutations, not by the fusion, NUP98::NSD1 without FLT3-ITD loses its prognostic significance — the confound that undermines the fusion's own reputation, Why a nucleoporin fusion needs menin-MLL1: the second menin-dependent fusion family, and what it borrows rather than carries
424. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 38612531
     Infant Acute Lymphoblastic Leukemia-New Therapeutic Opportunities

     Kulczycka M, Derlatka K, Tasior J, et al. · International Journal of Molecular Sciences 2024
     used by Infant acute lymphoblastic leukaemia (ALL diagnosed under 1 year of age)
425. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38513239
     Landscape of driver mutations and their clinical effects on Down syndrome-related myeloid neoplasms

     Sato T, Yoshida K, Toki T, et al. · Blood 143:2627-2643 2024
     used by IRX1 expression in KMT2A-rearranged paediatric AML is a FAB-M7 megakaryoblastic property, not a fusion property: 13 of 20 M7 versus 2 of 96 M5, and non-KMT2A-r M7 is 54 of 97, IRX1 is reported as expressed in AML subsets, so its absence from oncoprotein occupancy outside KMT2A::AFF1 is not an absence of IRX1
426. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38555405
     A complex interplay of intra- and extracellular factors regulates the outcome of fetal- and adult-derived MLL-rearranged leukemia

     Jassinskaja M, Ghosh S, Watral J, Davoudi M, Claesson Stern M, Daher U, Eldeeb M, Zhang Q, et al. · Leukemia 2024
     used by ITGA4 (VLA-4) and NG2 — the niche-adhesion axis of KMT2A-rearranged B-ALL, and the one approved drug that hits it
427. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38448574
     Guiding the HBO1 complex function through the JADE subunit.

     Gaurav N, Kanai A, Lachance C, Cox KL, Liu J, et al. · Nat Struct Mol Biol 2024
     used by JADE3 / PHF16 (Q92613) - the HBO1-complex scaffold with the strongest pan-fusion evidence in this beat, and an independent published contact with MLL
428. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38905635
     Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias

     Kwon MC, Thuring JW, Querolle O, Dai X, Verhulst T, Pande V, et al. · Blood 2024
     used by Johnson & Johnson / Janssen — bleximenib (JNJ-75276617): paediatric from age 2, but not infants, and the dedicated child study was withdrawn, Kura Oncology — ziftomenib (KO-539): an adults-only sponsor that quietly supplies infant trials, Menin dependence of KMT2A::MLLT1: real, repeatedly demonstrated, and always as one lane of a partner panel
429. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39256555
     Calcium modulates the tethering of BCOR-PRC1.1 enzymatic core to KDM2B via liquid-liquid phase separation

     Chen R, Zhang Y, Wang X, et al. · Communications Biology 2024
     used by KDM2B — 513 potent ChEMBL rows that are mostly patent bins, and no structure of the domain they claim to inhibit, PRC1.1 — the complex this graph has been leaning on, now enumerated subunit by subunit, and the enumeration changes the conclusion
430. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38819218
     CRISPR Dependency Screens in Primary Hematopoietic Stem Cells Identify KDM3B as a Genotype-specific Vulnerability in IDH2- and TET2-mutant Cells.

     Waarts MR; Mowla S; Boileau M; Martinez Benitez AR; et al. · Cancer Discov 2024
     used by KDM3B - the H3K9me1/2 demethylase that sits on the KMT2A breakpoint cluster region and keeps it from rearranging, and the only leukaemia gene in this graph whose direction of effect flips between the myeloid and the lymphoid literature
431. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38877874
     Synergistic effects of the KDM4C inhibitor SD70 and the menin inhibitor MI-503 against MLL::AF9-driven acute myeloid leukaemia

     Zhu W, Ding Y, et al. · British Journal of Haematology 2024
     used by KDM4C (JMJD2C/GASC1) — recruited by the retained KMT2A N-terminus, drugged in a KMT2A::AFF1 line, and invisible to CRISPR
432. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38101400
     Distinct roles of hematopoietic cytokines in the regulation of leukemia stem cells in murine MLL-AF9 leukemia

     Li Y, Seet CS, Mack R, et al. · Stem Cell Reports 2024
     used by KITLG (stem cell factor) - the niche ligand of KIT, zero mentions anywhere in this graph, and its own symbol collides with the SCF ubiquitin ligase this corpus talks about constantly
433. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39385230
     Enhancer looping protein LDB1 modulates MYB expression in T-ALL cell lines in vitro by cooperating with master transcription factors

     Li Y, Zhang Y, Yu Y, et al. · Journal of Experimental & Clinical Cancer Research 2024
     used by LDB1::KMT2A - the clearest statement in this literature that a sarcoma fusion keeps KMT2A exons 4 to 36 and discards exons 1 to 3
434. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38191578
     PSIP1/LEDGF reduces R-loops at transcription sites to maintain genome integrity.

     Jayakumar S, Patel M, et al. · Nat Commun 2024
     used by LEDGF as a survival factor rather than a tether: it is upregulated in chemoresistant AML blasts, protects against daunorubicin, and knocking it down sensitises MLLr lines, PSIP1 keeps R-loops off the genes it sits on, and removing it causes transcription-replication conflict, DNA damage and PARP-inhibitor sensitivity, The bite-back surface: LEDGF tethers CtIP to active chromatin and is required for DNA-end resection and homologous recombination
435. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39031937
     Fragment-based discovery of small molecule inhibitors of the HDGFRP2 PWWP domain.

     Wei X, Li S, et al. · FEBS Lett 2024
     used by LEDGF PWWP chemistry exists after all - 68 fragment hits, double-digit micromolar leads - and the pocket has a structural ceiling the NSD PWWPs do not
436. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38321106
     LIN28B promotes differentiation of fully transformed AML cells but is dispensable for fetal leukemia suppression.

     · Leukemia 2024
     used by LIN28B - a one-row BioID prey of KMT2A that a 2026 Blood paper shows is REQUIRED for KMT2A::AFF1 to transform human fetal cells, LIN28B has THREE published signs in myeloid leukaemia - oncogene, tumour suppressor, and differentiation agent - and the design quality runs opposite to the direction the index-fusion story needs, LIN28B-dependent fetal B- and NK-lymphopoiesis - the NORMAL state the leukaemia requirement is parasitic on, and the reason the therapeutic window is narrow by construction, PROPOSED: swap the partner, hold everything else - KMT2A::MLLT3 versus KMT2A::AFF1 in LIN28B-null human fetal liver CD34+ cells, PUBLISHED, DONE: human fetal liver CD34+ cells fail to transform on KMT2A::AFF1 induction without LIN28B (Ling et al., Blood 2026) - a dedicated human index-fusion experiment, read from the abstract only, Targeting LIN28B - the essential-function and wrong-sign risks are established by the SAME paper that makes it interesting, and the sign may reverse with lineage, The fetal state is PERMISSIVE for lymphoid KMT2A-fusion transformation and PROTECTIVE against myeloid - which is why LIN28B has opposite signs in the two literatures, Two groups invoke LIN28B to explain the SAME epidemiological fact in OPPOSITE directions - and neither claim is the one this graph has been repeating
437. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38272888
     Genetics and pathologic landscape of lineage switch of acute leukemia during therapy

     Zhou T, Curry CV, Khanlari M, Shi M, Cui W, et al. · Blood Cancer Journal 2024
     used by Lineage switch as antigen escape from CD19-directed therapy in KMT2A-rearranged leukemia, Lineage switch in KMT2A-rearranged leukemia — the same clone changes what kind of blood cell it is
438. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38824932
     Iadademstat in combination with azacitidine in patients with newly diagnosed acute myeloid leukaemia (ALICE): an open-label, phase 2a dose-finding study

     Salamero O, Molero A, Pérez-Simón JA, et al. · Lancet Haematology 2024
     used by LSD1/KDM1A inhibition — a differentiation therapy with real clinical pharmacodynamics and no randomised proof
439. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38226414
     Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia

     Frett B, Stephens KE, Koss B, Melnyk S, Farrar J, Saha D, Roy Choudhury S · Cancer Science 115(3):963-973 2024
     used by MED12 - a named menin-associated protein that restrains menin's transcriptional output, and the anchor of the CDK8 module a KMT2A-r AML paper co-targets
440. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37890156
     Acute myeloid leukemias with UBTF tandem duplications are sensitive to menin inhibitors

     Barajas JM, et al. · Blood 143(7):619-630 2024
     used by Menin dependency tracks the availability of an intact menin-binding motif, in cis or in trans — not the fusion family
441. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39294124
     Multiomic single cell sequencing identifies stemlike nature of mixed phenotype acute leukemia

     Peretz CAC, Kennedy VE, Walia A, Delley CL, Koh A, et al. · Nature Communications 2024
     used by Mixed-phenotype acute leukemia and KMT2A rearrangement — plasticity caught in the act
442. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38990722
     YY1-mediated enhancer-promoter communication in the immunoglobulin μ locus is regulated by MSL/MOF recruitment.

     Phongbunchoo Y, Braikia FZ, Pessoa-Rodrigues C, Ramamoorthy S, Ramachandran H, Grosschedl A, Ma F, Cauchy P, Akhtar A, Sen R, Mittler G, Grosschedl R · Cell Rep 2024
     used by MSL2 — the second H2B ubiquitin ligase, sitting inside the MOF complex the KMT2A fragment contacts
443. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38889007
     An enhancer RNA recruits KMT2A to regulate transcription of Myb

     Kim J, Diaz LF, Miller MJ, Leadem B, Krivega I, Dean A · Cell Reports 43(7):114378 2024
     used by MYB — rank 17 of 17,728 for KMT2A selectivity, and the only node in this beat where partial, transient suppression eradicated leukaemia without stopping normal blood production
444. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.reviewPMID 39682203
     Synergistic Strategies for KMT2A-Rearranged Leukemias: Beyond Menin Inhibitor

     See PubMed record PMID 39682203 for the full author list (not transcribed here) · Cancers (Basel) 2024
     used by MYC reactivation through PRC1.1 loss — a named, druggable bypass out of menin dependence
445. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39216515
     An Atypical Mechanism of SUMOylation of Neurofibromin SecPH Domain Provides New Insights into SUMOylation Site Selection.

     Bergoug M, Mosrin C, Serrano A, Godin F, Doudeau M, Dundović I, Goffinont S, Normand T, Suskiewicz MJ, Vallée B, Bénédetti H · J Mol Biol 2024
     used by NF1 - the only tumour-suppressor loss in this disease, and it is a deletion, so a mutation panel cannot see it
446. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39192759
     Clinical relevance of NFYA splice variants in patients with acute myeloid leukaemia undergoing intensive chemotherapy.

     Yang YT, Yao CY, Kao CJ, Chiu PJ, Lin ME, Hou HA, Lin CC, Chou WC, Tien HF · Br J Haematol 2024
     used by NFYC / NF-YC - a histone-fold transcription factor whose partner subunit carries an H2B-like ubiquitination, and the most selective of the eleven TF baits that reached KMT2A
447. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.preprintPMID 38352423
     Cohesin loss and MLL-AF9 are not synthetic lethal in murine hematopoietic stem and progenitor cells.

     Meyer A, Stelloh C, Zhu N, Rao S · Research Square 2024
     used by NIPBL - the cohesin loader, the cleanest degron result in the whole architecture literature, and a second bounded absence in this disease, RAD21 - the cohesin subunit with the most break-prone sites in KMT2A-rearranged patients, and the degron experiment this graph keeps asking for, SMC1A - a bounded absence written with its query: eleven records, none about this disease, and the whole literature is Cornelia de Lange syndrome, SMC3 - the cohesin ATPase arm, the only subunit whose partial loss has been tested directly against a KMT2A fusion, and it was tolerated, STAG2 - the cohesin subunit that defines secondary AML, and the one whose loss a KMT2A fusion does not care about
448. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38519032
     The balance between nuclear import and export of NLRC5 regulates MHC class I transactivation.

     · J Biol Chem 2024
     used by NLRC5 - the MHC class I transactivator, and the route by which interferon activates class I when KMT2A and KMT2B are both gone
449. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39277599
     Orientia tsutsugamushi Ank5 promotes NLRC5 cytoplasmic retention and degradation to inhibit MHC class I expression.

     · Nat Commun 2024
     used by NLRC5 - the MHC class I transactivator, and the route by which interferon activates class I when KMT2A and KMT2B are both gone
450. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39182032
     NUP98::NSD1 and FLT3/ITD co-expression is an independent predictor of poor prognosis in pediatric AML patients

     Wang JW, et al. · BMC Pediatrics 2024
     used by NUP98::NSD1 without FLT3-ITD loses its prognostic significance — the confound that undermines the fusion's own reputation
451. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38295280
     Prognostic impact of cooccurring mutations in FLT3-ITD pediatric acute myeloid leukemia

     Tarlock K, et al. · Blood Advances 2024
     used by NUP98::NSD1 without FLT3-ITD loses its prognostic significance — the confound that undermines the fusion's own reputation
452. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39585385
     The second adult case of NUTM1 fusion-positive B-cell lymphoblastic leukemia: A recurring pattern of poor prognosis

     Chen X, Ma X, Yuan L, et al. · Annals of Hematology 2024
     used by NUTM1-rearranged B-ALL - the KMT2A-wild-type arm of the same infant trials, with 4-year EFS of 100% against 36-37% next door
453. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37743097
     Treatment outcomes of childhood PICALM::MLLT10 acute leukaemias.

     Mark C, et al. · Br J Haematol 2024
     used by Outcome in PICALM::MLLT10: children with ALL do reasonably well, children with AML do badly, and transplant does not rescue them, PICALM::MLLT10 (CALM-AF10), t(10;11)(p13;q14) - the DOT1L-dependent HOXA fusion that contains no KMT2A
454. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 38895061
     PICALM::MLLT10 may indicate a new subgroup of acute leukemias with miscellaneous immunophenotype and poor initial treatment response but showing sensitivity to venetoclax.

     Sun H, et al. · EJHaem 2024
     used by Outcome in PICALM::MLLT10: children with ALL do reasonably well, children with AML do badly, and transplant does not rescue them
455. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39505901
     Nucleolar Pol II interactome reveals TBPL1, PAF1, and Pol I at intergenic rDNA drive rRNA biogenesis.

     Khosraviani N, Yerlici VT, St-Germain J, Hou YY, Cao SB, Ghali C, Bokros M, Krishnan R, Hakem R, Lee S, Raught B, Mekhail K · Nat Commun 2024
     used by PAF1 is annotated as punctate everywhere in the nucleus EXCEPT the nucleolus - and a 2024 proximity map puts it in the nucleolus
456. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38429501
     Genomic and global gene expression profiling in pediatric and young adult acute leukemia with PICALM::MLLT10 Fusion.

     Ma J, et al. · Leukemia 2024
     used by PICALM::MLLT10 (CALM-AF10), t(10;11)(p13;q14) - the DOT1L-dependent HOXA fusion that contains no KMT2A, The focal half: H3K79 hypermethylation at the HOXA cluster and MEIS1 - but which cluster member differs between CALM-AF10 and MLL-AF10
457. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39684470
     Only Infant MLL-Rearranged Leukemia Is Susceptible to an Inhibition of Polo-like Kinase 1 (PLK-1) by Volasertib

     · International Journal of Molecular Sciences 2024
     used by PLK1 — nominated as an infant-restricted vulnerability, and one of the most essential genes in the genome, The adult-type model answers PLK1 inhibition by making more PLK1 and AURKA, Volasertib against PLK1: a differential window claimed in infant-type cells, on a target every dividing cell needs
458. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39587079
     Cryo-EM structure of PML RBCC dimer reveals CC-mediated octopus-like nuclear body assembly mechanism

     Tan Y, Li J, Zhang S, Zhang Y, Zhuo Z, Ma X, Yin Y, Jiang Y, Cong Y, Meng G · Cell Discov 10:118 2024
     used by PML — domain architecture and residue coordinates
459. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38724444
     Towards the Targeted Protein Degradation of PRMT1.

     Martin PL, et al. · ChemMedChem 2024
     used by PRMT1 — an MLL-fusion cofactor whose first-in-human inhibitor was terminated for lack of efficacy and toxicity
460. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39513743
     The uncharacterized protein ZNF200 interacts with PRMT3 and aids its stability and nuclear translocation.

     Gupta S, Verma M, Kadumuri RV, Chutani N, Khan MIK, Chavali S · Biochemical Journal 2024
     used by PRMT3 - the mostly-cytoplasmic ribosome methyltransferase that also writes the ACTIVATING mark on the residue PRMT5 represses, has an acute-leukaemia degrader, and is invisible to this project's own mark-query rule
461. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39120042
     Discovery of PRMT3 Degrader for the Treatment of Acute Leukemia.

     Zou W, Li M, Wan S, Ma J, Lian L, Luo G, Zhou Y, Li J, Zhou B · Advanced Science 2024
     used by PRMT3 - the mostly-cytoplasmic ribosome methyltransferase that also writes the ACTIVATING mark on the residue PRMT5 represses, has an acute-leukaemia degrader, and is invisible to this project's own mark-query rule
462. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39485844
     A dual role for PSIP1/LEDGF in T cell acute lymphoblastic leukemia.

     Demoen L, Matthijssens F, et al. · Sci Adv 2024
     used by PSIP1 is a tumour suppressor in the lymphoid lineage next door: losing Psip1 ACCELERATES T-ALL in mice, while the same protein is a dependency in KMT2A-rearranged myeloid leukaemia
463. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39033241
     Subunit-specific analysis of cohesin-mutant myeloid malignancies reveals distinct ontogeny and outcomes.

     Jann JC, Hergott CB, Winkler M, Liu Y, Braun B, Charles A, et al. · Leukemia 2024
     used by RAD21 - the cohesin subunit with the most break-prone sites in KMT2A-rearranged patients, and the degron experiment this graph keeps asking for, SMC1A - a bounded absence written with its query: eleven records, none about this disease, and the whole literature is Cornelia de Lange syndrome, SMC3 - the cohesin ATPase arm, the only subunit whose partial loss has been tested directly against a KMT2A fusion, and it was tolerated
464. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.reviewPMID 38577935
     Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review).

     Zhan Y, Yin A, Su X, Tang N, Zhang Z, Chen Y, et al. · Int J Mol Med 2024
     used by RBBP7 - the silent paralogue that is not silent, and the reason this project's paralogue rule finally produced a positive answer
465. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
     EU/3/23/2881 - orphan designation for treatment of acute myeloid leukaemia (ziftomenib)

     European Medicines Agency, Committee for Orphan Medicinal Products · EMA orphan designations register 2024
     used by Repairing 85 defective citation blocks, and the finding that the queue's own numbers were wrong in three directions at once
466. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.regulatory
     FDA approves revumenib for relapsed or refractory acute leukemia with a KMT2A translocation

     US Food and Drug Administration · FDA Oncology (Cancer) Approval Notifications 2024
     used by Revumenib (SNDX-5613, Revuforj) — first approved menin–KMT2A interface inhibitor, The rare paediatric disease priority review voucher: a $150-200m bearer bond, lapsed for 14 months, now live to 2029
467. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.journal-articlePMID 38173411
     Histone Trimethylations and HDAC5 Regulate Spheroid Subpopulation and Differentiation Signaling of Human Adipose-Derived Stem Cells.

     Chang MM, Hong YK, Hsu CK, et al. · Stem Cells Transl Med 2024
     used by Revumenib does not move H3K27me3 in MLL-fusion leukaemia, in vitro or in vivo: the absence narrows a THIRD time and the experiment's prior collapses
468. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     NCBI GEO series GSE210480 supplementary file listing and filelist.txt (Gray et al. 2023, Cell), retrieved 2026-09-22

     NCBI Gene Expression Omnibus · NCBI GEO 2024
     used by Run in coordinates: the protective CTCF site and the patient break-prone window are ONE element, it is cohesin-bound, and the 'functional cut point' is 3.75 kb away - two of the graph's three exon-11s were the same exon and the third was not
469. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
     A Phase 1/2 Trial of Uproleselan Combined With High Dose Busulfan Pre-Transplant Conditioning in Hematopoietic Stem Cell Transplantation for Patients With Chemotherapy Resistant Acute Myeloid Leukemia

     · ClinicalTrials.gov 2024
     used by SELE (E-selectin) - the vascular-niche chemoresistance receptor with a clinical antagonist, zero KMT2A papers, and a paediatric trial that a company restructuring closed
470. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38971831
     Epigenetic maintenance of adult neural stem cell quiescence in the mouse hippocampus via Setd1a.

     Zhao T, Hong Y, Yan B, Huang S, Ming GL, Song H · Nat Commun 2024
     used by SETD1A — a leukemia dependency whose enzyme activity turns out to be dispensable
471. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39689172
     Histone methyltransferase SETDB1 safeguards mouse fetal hematopoiesis by suppressing activation of cryptic enhancers.

     Kazerani M, Cernilogar F, Pasquarella A, Hinterberger M, et al. · Proceedings of the National Academy of Sciences 2024
     used by SETDB1 (Q15047, KMT1E/ESET) - the second H3K9me3 writer: it represses the fusion's own targets via the PAF1 complex, it is required in fetal liver HSPCs and in leukaemic stem cells, and it is a broad dependency in half the CRISPR panel - three published directions that do not agree
472. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38048593
     Transcriptional control of leukemogenesis by the chromatin reader SGF29.

     Barbosa K, Deshpande A, et al., Deshpande AJ · Blood 2024
     used by SGF29 — a SAGA reader with a Tudor pocket, intermediate essentiality, and the best unexploited profile in this beat
473. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38233109
     Regularly spaced tyrosines in EBF1 mediate BRG1 recruitment and formation of nuclear subdiffractive clusters.

     Zolotarev N, Wang Y, Du M, Bayer M, Grosschedl A, Cisse I, Grosschedl R · Genes Dev 2024
     used by SMARCA4 (BRG1) - a tumour suppressor by mutation and a maintenance requirement by knockdown, and in KMT2A-rearranged lines the dependency data say it is not selective at all
474. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38730645
     Genomic Characterization of Partial Tandem Duplication Involving the KMT2A Gene in Adult Acute Myeloid Leukemia

     Seto A, Downs G, King O, Salehi-Rad S, Baptista A, Chin K, Grenier S, Nwachukwu B, Tierens A, Minden MD, Smith AC, Capo-Chichi JM · Cancers 2024
     used by Step 3: the G-banded karyotype and t(4;11)(q21;q23)
475. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 39011567
     Roles of Menin in T cell differentiation and function: Current knowledge and perspectives.

     Zhou P, Liu W, Ma J · Immunology 2024
     used by Th17 cell - the mature CD4 T-helper subset whose differentiation and maintenance require MENIN, which makes it the clearest published on-target normal-tissue liability of the menin interface
476. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     BigTools / pybigtools - a Rust library and Python bindings for the BigWig and BigBed (BBI) formats; installation and remote-read behaviour verified on this host 2026-09-22

     Huey JD, Kaplan N (BigTools project) · PyPI / GitHub 2024
     used by The bigWig refusal of cycle 57 is overturned: pybigtools installs on this box under Python 3.12, reads GEO tracks by HTTP range request without downloading them, and passes the control loci the refusal itself demanded
477. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37902585
     MEIS inhibitors reduce the viability of primary leukemia cells and Stem cells by inducing apoptosis

     Meric N, Albayrak E, Gulbas Z, Kocabas F · Leukemia & Lymphoma 65:187-198 2024
     used by The druggable node in the homeodomain code is the MEIS1-PBX3 interface, not the HOX-PBX one - and it is the only one nobody has attacked
478. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     Blockade of the lncRNA-DOT1L-LAMP5 axis: H3K79me2 and H3K79me3 ChIP in MOLM-13 (GSE150483)

     GEO submitters · NCBI Gene Expression Omnibus 2024
     used by The lncRNA-DOT1L-LAMP5 axis was measured on H3K79 in MOLM-13 alone: eight human samples, one fusion, no index-fusion arm
479. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39609309
     Sarcomas arising in MEN1 patients: demonstrating LOH of the MEN1 locus and loss of menin expression.

     van Leeuwaarde RS, Halfdanarson TR, Sudhakar SM, et al. · Fam Cancer 2024
     used by The predictable clinical error this beat exists to prevent: a menin inhibitor given for a KMT2A-rearranged sarcoma because of the gene name
480. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 38403586
     Analysis of the first ten years of FDA's rare pediatric disease priority review voucher program: designations, diseases, and drug development

     Mease C, Miller KL, Fermaglich LJ, Best J, Liu G, Torjusen E · Orphanet Journal of Rare Diseases 19(1):86 2024
     used by The rare paediatric disease priority review voucher: a $150-200m bearer bond, lapsed for 14 months, now live to 2029
481. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38636717
     Identification of a novel histone H2A mono-ubiquitination-inhibiting cell-active small molecule.

     Ni S, Takada Y, Ando T, Yu S, Yamashita Y, Takahashi Y, et al. · Bioorg Med Chem Lett 2024
     used by There is no selective PRC1 catalytic inhibitor - the entire chemistry is one 2013 tool compound and its analogues, and it hits both paralogues by design
482. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39116419
     Pediatric therapy-related hematologic neoplasms show enrichment for KMT2A rearrangement and lymphoblastic phenotype.

     Kovach AE, Komova D, Itov A, et al. · Leukemia & Lymphoma 2024
     used by TP53 - named in 84 entries of this graph, absent from the index genome study of the disease, and four different things depending on when you look
483. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38734786
     TIF1beta activates leukemic transcriptional program in HSCs and promotes BCR::ABL1-induced myeloid leukemia.

     Morii M, Kubota S, Iimori M, Yokomizo-Nakano T, Hamashima A, et al. · Leukemia 2024
     used by TRIM28 / KAP1 / TIF1beta (Q13263) - the KRAB-ZFP corepressor scaffold in the pan-MLL-fusion core, with the weakest index-fusion p-value but a leukaemic role in another fusion family
484. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.journal-articlePMID 39205150
     A Truncated Isoform of Cyclin T1 Could Contribute to the Non-Permissive HIV-1 Phenotype of U937 Promonocytic Cells.

     Alberio T, Shallak M, Shaik AKB, Accolla RS, Forlani G · Viruses 2024
     used by U-937 (CVCL_0007) - the single line carrying this graph's menin-independence argument, and it is adult, monocytic, historically contaminated, and exists as two variants nobody here distinguishes
485. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 39661677
     MLL/WDR5 complex recruits centriolar satellite protein Cep72 to regulate microtubule nucleation and spindle formation.

     Chodisetty S, Arora A, Malik KK, Goel H, Tyagi S · Sci Adv 2024
     used by WDR5 and KMT2A are at the centrosome and the midbody - a non-chromatin address for both, with a patient-cell phenotype
486. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38822412
     Sequential drug treatment targeting cell cycle and cell fate regulatory programs blocks non-genetic cancer evolution in acute lymphoblastic leukemia.

     Malyukova A, Lahnalampi M, Falqués-Costa T, Pölönen P, Sipola M, Mehtonen J, et al. · Genome Biol 2024
     used by WEE1 - the one checkpoint target with a KMT2A::AFF1-specific result, and the paper that also found the escape route
487. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38747396
     Structural studies of intrinsically disordered MLL-fusion protein AF9 in complex with peptidomimetic inhibitors.

     Yang Y, Ahmad E, et al. · Protein Sci 2024
     used by What this beat searched, read and set aside - including one cell line the accession database has not caught up with, and one query that returns a clean zero
488. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38616361
     Characteristics and treatment of acute myeloid neoplasms with cutaneous involvement in infants up to 6 months of age: A retrospective study

     Renaud J, Goemans BF, Locatelli F, Pigazzi M, Redmond S, et al. · Pediatric Blood & Cancer 2024
     used by Where KMT2A-rearranged leukemia physically sits — marrow niche, CNS, blood, liver/spleen and skin
489. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38096371
     Mezigdomide is effective alone and in combination with menin inhibition in preclinical models of KMT2A-r and NPM1c AML

     Bourgeois W, Cutler JA, Aubrey BJ, et al. (Armstrong SA, senior author) · Blood 143(15):1513-1527 2024
     used by Which step is rate-limiting, and what compensates when you block it — the bite-back map for the causal chain
490. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38917791
     C646 degrades Exportin-1 to modulate p300 chromatin occupancy and function.

     Chen YF, Rahman A, Sax JL, Atala Pleshinger MJ, Friedrich RM, Adams DJ · Cell Chem Biol 2024
     used by XPO1 / exportin-1 (CRM1) - the cell's main nuclear export receptor, and a chromatin-bound transcriptional scaffold
491. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38975722
     YAP1::KMT2A fusion-positive sarcoma: An emerging soft tissue tumor entity with morphological features resembling a sclerosing epithelioid fibrosarcoma.

     Agarwal A, Rekhi B, Goel V, Bajpai J, Rastogi S · Indian J Pathol Microbiol 2024
     used by YAP1 (P46937) - the Hippo pathway's transcriptional co-activator, and a KMT2A fusion partner from a completely different functional class
492. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 39258225
     Acute myeloid leukemia with a ZMYND11::MBTD1 fusion gene following chemotherapy and radiotherapy for breast cancer: A case report

     Kawai H, Shiraiwa S, Ogiya D, et al. · Leukemia Research Reports 2024
     used by ZMYND11::MBTD1, t(10;17)(p15;q21) - a chromatin reader welded to the NuA4/TIP60 acetyltransferase, maintaining Hoxa/Meis1/Myb/Myc/Sox4 in AML: the KMT2A-fusion architecture built from different parts
493. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38961301
     Targeting pericentric non-consecutive motifs for heterochromatin initiation.

     Ma R, Zhang Y, Zhang J, Zhang P, Liu Z, Fan Y, Wang HT, Zhang Z, Zhu B · Nature 2024
     used by ZNF512 (Q96ME7) - the one protein of the nine deferred pan-MLL-fusion preys that is a sequence-specific chromatin factor, and it initiates pericentric heterochromatin
494. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36996387
     Measurable Residual Disease and Fusion Partner Independently Predict Survival and Relapse Risk in Childhood KMT2A-Rearranged Acute Myeloid Leukemia: A Study by the International Berlin-Frankfurt-Münster Study Group.

     van Weelderen RE, Klein K, et al. · J Clin Oncol 2023
     used by 172 adults with KMT2A-r AML: translocation subtype did not predict survival, so treat all KMT2A-r as adverse, 756 children with 11q23/MLL-rearranged AML: 5-year EFS runs from 11% to 92% depending on the partner, AUGMENT-101: the partner composition of the trial that approved a menin inhibitor, with KMT2A::AFF1 at n=2 evaluable, CIBMTR post-transplant AML (n=426 KMT2A-r, curated cytogenetics): no outcome difference by fusion partner, COG AAML0531/1031 (n=2,080): MLLT10 fusions are adverse, and the 5-prime partner barely changes it, I-BFM childhood KMT2A-r AML (n=1,130): the 3-prime partner defines two risk groups that differ by 24 EFS points, Infant BCP-ALL (n=175): KMT2A::AFF1 2-year EFS 36% versus 37% for every other partner (P=0.9), KMT2A::MLLT1 is high-risk in childhood AML and the best-outcome cell in childhood T-ALL: the partner effect changes sign with lineage, KMT2A::MLLT3 / t(9;11): the best-known partner prognosis claim, and the three cohorts that did not reproduce it, KMT2A::MLLT3 across 612 genotyped patients: myeloid at every age, but 248 of them have ALL, and 157 of those are infants, Ponte-di-Legno non-infant KMT2A-r ALL (n=629): 5-year EFS spans 41.7% to 91.2% across partner-by-lineage cells, The analysis that would settle it: a partner-by-lineage interaction term in pooled individual-patient data, The clinical outcome data do not support a single KMT2A class, and they do not refute the menin interface either, The lineage confound: partner predicts whether the leukaemia is myeloid or lymphoid before it predicts anything else
495. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 36256911
     Outcomes of Childhood Noninfant Acute Lymphoblastic Leukemia With 11q23/KMT2A Rearrangements in a Modern Therapy Era: A Retrospective International Study.

     Attarbaschi A, Möricke A, et al. · J Clin Oncol 2023
     used by 172 adults with KMT2A-r AML: translocation subtype did not predict survival, so treat all KMT2A-r as adverse, Infant BCP-ALL (n=175): KMT2A::AFF1 2-year EFS 36% versus 37% for every other partner (P=0.9), KMT2A::MLLT1 is high-risk in childhood AML and the best-outcome cell in childhood T-ALL: the partner effect changes sign with lineage, KMT2A::MLLT3 / t(9;11): the best-known partner prognosis claim, and the three cohorts that did not reproduce it, KMT2A::MLLT3 across 612 genotyped patients: myeloid at every age, but 248 of them have ALL, and 157 of those are infants, Ponte-di-Legno non-infant KMT2A-r ALL (n=629): 5-year EFS spans 41.7% to 91.2% across partner-by-lineage cells, The age confound: a partner arm and an age arm are nearly the same arm, The analysis that would settle it: a partner-by-lineage interaction term in pooled individual-patient data, The clinical outcome data do not support a single KMT2A class, and they do not refute the menin interface either, The experiment: cross-tabulate MLLT1 breakpoint class against age, lineage and outcome in the Frankfurt archive, then confirm reciprocal status by RNA in whoever has it, The lineage confound: partner predicts whether the leukaemia is myeloid or lymphoid before it predicts anything else, The protocol and era confound: the partner datasets span 1983 to 2016 and outcome moved under them, Which partner, in which patient: KMT2A partner frequencies across six age-lineage strata
496. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 37202521
     Structural basis for Lewis antigen synthesis by the alpha1,3-fucosyltransferase FUT9.

     Kadirvelraj R, Boruah BM, Wang S, Chapla D, Huang C, Ramiah A, et al. · Nat Chem Biol 2023
     used by A CD number names a reagent cluster, not a molecule - and four different things can sit behind one, CD15 (Lewis-x, SSEA-1, 3-fucosyl-N-acetyllactosamine) - a sugar, not a protein: the most-named antigen in this graph that no gene encodes, FUT9 - the dedicated Lewis-x synthase, structurally solved, and untouched by the KMT2A literature
497. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 37717054
     Genome-wide analysis of DNA-PK-bound MRN cleavage products supports a sequential model of DSB repair pathway choice.

     Deshpande RA, Marin-Gonzalez A, Barnes HK, et al. · Nature Communications 2023
     used by A genome-wide DAMAGE-STATE occupancy dataset for CtIP and MRE11 does exist and is public - GSE218590, 58 samples, +/- 4-OHT and a light-activated Cas9 time course - and it cannot answer the KMT2A question, because there is not one AsiSI site in the 90,377 bp of the gene
498. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 36922589
     MEN1 mutations mediate clinical resistance to menin inhibition

     Perner F, Stein EM, Wenge DV, Singh S, Kim J, Apazidis A, et al., Levine RL, Armstrong SA, Cai SF · Nature 615(7954):913-919 2023
     used by A genome-wide peak-call census is the wrong pharmacodynamic assay for a menin inhibitor, in two independent ways, A pocketless fusion already had its protein-protein-interface drug taken to phase I/II - and TK216 turned out to be a microtubule destabiliser, not an EWS::FLI1 antagonist. This is the closest thing the field has to a controlled failure of the interface hypothesis., Agency law — actual authority, apparent authority, and what revocation cannot undo, Analysis (runnable): build the first correlation matrix of menin-inhibitor resistance routes, from screens and from patient cohorts, BCR::ABL1 (Philadelphia chromosome), t(9;22)(q34;q11), Bounded absence: no published study has tested whether a KMT2A fusion GAINS chromatin sites under a menin inhibitor - and the same pipelines found gains for two other proteins when they looked, Census of every published chromatin-occupancy measurement made under a menin inhibitor: eight datasets, every one TSS-anchored, every one tabulating losses only, Collaborate or compete: an honest matrix, including where the lab would be duplicating a better-resourced effort, Covalent or reversible is the axis on which ‘the menin inhibitor class’ most plausibly breaks, Eviction is a claim about menin. The field, and this graph, transfer it to the fusion without a measurement that supports the transfer, Experiment: does a MEN1 resistance mutant pay a price when the drug is not there? The competition assay nobody has run, Experiment: map what stays on chromatin when the menin inhibitor has done everything it can do, Experiment: put the resistant and the sensitive fusion side by side - if a MEN1 interface mutant keeps the fusion in place while the wild type moves it, relocation is real and menin is what chooses the address, Experiment: spike-in-calibrated, fusion-attributable occupancy of KMT2A::AFF1 in the first 24 hours of menin inhibition, scored for gains as well as losses, Hypothesis — forced-oligomerisation interfaces are the mutation-resistant drug targets the fusion field has been ignoring, Hypothesis: a defined subset of fusion binding sites survives saturating menin inhibition on menin-independent tethering, and that residual set is where bypass resistance comes from, Hypothesis: adaptive scheduling of menin inhibitors will fail, because MEN1 resistance mutations probably cost the cell nothing, Hypothesis: the ceiling on menin-interface disruption is cell-state plasticity, not target mutation, JUND liberation — the drug's mechanism of action and one of its mechanisms of resistance are the same event, Mechanism class 1 — chromatin and elongation hijack (KMT2A-r, NUP98-r), MEN1 / menin — the adaptor the fusion cannot work without, MEN1 drug-interface mutations — the first proof that a chromatin drug can drive Darwinian escape in patients, Model: resistance-mutation prediction - cannot be trained. There are six patient-observed labels in the world, and a base-editor screen already does the job better, NUP98 fusions share the menin dependency (confirmed preclinically) — and the partner-supplied reader/writer module is not why, Only a handful of loci lose fusion occupancy under a menin inhibitor, and they are the same few whether menin is drugged or deleted: MEIS1, MEF2C, JMJD1C - not HOXA, not MYB, Phase-2 dossier: the non-small-molecule modalities - degraders first, and the honest limits of each, Risk: the class's pharmacodynamic logic measures menin and reports it as the fusion, in a drug class dosed in infants, Scott Armstrong & Andrei Krivtsov (Dana-Farber / Boston Children's) — the group that turned menin dependency into a drug, Switching menin inhibitors: four substitutions defeat all of them, three defeat only some, and the map now exists, The clearest clinical rationale for a LEDGF agent - second line after menin-inhibitor failure - has never been tested, and one 2025 measurement now argues against it, The experiment that closes the LEDGF hole: doxycycline-inducible PSIP1 knockdown switched on AFTER a human KMT2A::AFF1 xenograft is established, The gain question is answerable today for free: GSE127508 contains MLL1n ChIP-seq in a fusion-only line, plus and minus VTP-50469, and nobody has called peaks on the treated sample, The LEDGF IBD–KMT2A grip: the second half of the clamp, and nobody is drugging it, The menin inhibitor removes three-quarters of the fusion from its own promoters, replicated in two batches, The menin–KMT2A grip (MBM1), the interface the drugs actually block, The pivotal menin-inhibitor paper reports that the drug does NOT globally displace MLL1 or the fusion from chromatin - menin goes, the fusion largely stays, Three routes to one observation: the CUT&RUN panel that says whether menin eviction, H3K36me3 loss or MLL loss takes LEDGF off the fusion's genes, Where does the fusion go when menin inhibition evicts it? Almost nobody has looked - the published readouts are chromatin occupancy, the one protein whose fate was measured properly is menin, and the single human observation of fusion loss is confounded by a lineage switch, Which step is rate-limiting, and what compensates when you block it — the bite-back map for the causal chain, Why BCR::ABL1 became treatable — and what KMT2A::AFF1 does not share with it, ZFP64 — rank 4 on selectivity, and there is not even a ChEMBL entry for it
499. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37627154
     Menin Maintains Cholesterol Content in Colorectal Cancer via Repression of LXR-Mediated Transcription.

     Nyul TE, et al. · Cancers (Basel) 2023
     used by A menin inhibitor is a partial LXR agonist, and no trial in the class has looked, Measure ABCA1, ABCG1 and SREBF1 before and during menin inhibition - a three-transcript panel on samples that already exist, Menin is a corepressor of the LXR sterol sensors - one paper supplies three of this graph's twelve missing partners, and the function has never been written down here, NR1H3 / LXR-alpha - the best-observed of the three MEN1 sterol partners, with both directions curated in two species, and menin as its corepressor
500. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 37019990
     The KMT2A recombinome of acute leukemias in 2023.

     Meyer C, Larghero P, Almeida Lopes B, et al. · Leukemia 2023
     used by A reciprocal-negative t(11;19) patient was documented in 1995 by a different mechanism entirely - the 3' half of KMT2A was simply deleted, About one KMT2A-rearranged patient in twenty has no direct fusion at all - only the reciprocal one, ACER1 is on the list of in-frame reciprocal KMT2A partners - and ACER1 is the gene the 'reciprocal-negative' breakpoints fall next to, AFDN / AF6 — domain architecture and residue coordinates, Analysis (runnable): do KMT2A partners rank by nuclear contact frequency in the same order as they rank in patients?, Analysis (runnable): does product viability leave a signature in the KMT2A breakpoint map once DNA fragility is controlled for?, Analysis (runnable): is anything actually enriched at KMT2A breakpoints? The test has never been run against a background that could say no, Analysis (runnable): mine the KMT2A junction sequences for repair-pathway signature, and count the one junction class with a genetic control behind it, Analysis: is the KMT2A genomic breakpoint a prognostic variable? A reanalysis of data Interfant and Frankfurt already hold, Anti-ELL antibodies carry a confound the other partners do not: two paralogues and a protein whose abundance is actively regulated, Anti-ENL antibodies are the cleanest partner reagent in this disease and sit on top of the worst confound, At the DNA level almost every KMT2A-rearranged patient has a reciprocal allele - 94% across partners, and 5% have nothing else, Attribution audit 5 of 5 - where KMT2A::AFF1 sits on chromatin: the field's standard attribution heuristic is invalidated by the paper that founded it, but two real survivors exist, Breakpoint anatomy, and an audit of the prognosis claim, Collaborate or compete: an honest matrix, including where the lab would be duplicating a better-resourced effort, Competing model 2: the reciprocal allele is lost as the leukaemia evolves, and losing it selects for something worse, Competing model 3: reciprocal status is a proxy for where the break fell, and the thing that changed is the DIRECT product, CTCF/cohesin occupancy at the KMT2A exon-11 anchor is both the cause of the break and the chaperone of its correct repair - so losing it gives FEWER breaks and MORE rearrangements, Do different breaks give different biology? A verdict on partner identity vs breakpoint position, Each partner prefers a different KMT2A exon: partner-specific break position in 3,401 patients, ELL2 — domain architecture and residue coordinates, Experiment: bait the KMT2A breakpoint cluster region and sequence everything it joins to, in a fetal-like human progenitor, Experiment: does AF1q self-associate, and does KMT2A::MLLT11 transform? The two measurements nobody has made on the 10th most common KMT2A fusion, GAS7 — growth-arrest-specific F-BAR protein, the second pillar of the forced-oligomerisation model, Half of all KMT2A::MLLT1 patients make no reciprocal product at all - a ready-made control arm of about 240 people, How a chromosome translocation actually forms: proximity + breakage + repair, How a spliced fusion works: the break lands in front of MLLT1, the gene is never cut, and there is nothing left to make a reciprocal product from, Hypothesis: the KMT2A breakpoint map is shaped by product viability, not only by DNA fragility, and the signature is that breaks respect inter-domain linkers, Hypothesis: the reciprocal AFF1::KMT2A product protects only when it is structurally complete, so its prognostic effect is a breakpoint class in disguise, In childhood t(11;19), every lymphoblastic case was MLLT1 and every ELL case was myeloid - the one rule that lets an old cohort be de-contaminated, Is reciprocal status or breakpoint position used in MRD design or risk stratification? Once, by necessity, in 16 of 3,401 patients - and nowhere in any risk model, Is the YEATS asymmetry just intron geometry? Computed from hg38: the direction is explained, the magnitude is not, and both genes fail the same prediction, Join the KMT2A breakpoint archive to the Interfant MRD and outcome database, on patient, Junction RT-PCR is the one routine assay in this disease that IS fusion-specific - and it is structurally blind to KMT2A*, KMT2A / MLL1 — the gene that breaks, KMT2A exon 11 / intron 11 breakpoints (BCR subregion C): the infant, HOXA-low, topoisomerase-II-associated break, KMT2A intron 9 / exon 9 breakpoints (BCR subregion A): the HOXA-high, older-patient break, KMT2A major breakpoint cluster region (BCR1): intron 7 - exon 13, ~8.3 kb, KMT2A minor breakpoint cluster region (BCR2): intron 20 - exon 24, KMT2A-rearranged acute leukemia across all ages: infants are 4% of it, KMT2A-rearranged acute lymphoblastic leukaemia, KMT2A::ABI1 (MLL-ABI1), t(10;11)(p11.2;q23) — the partner that binds an elongation partner, KMT2A::AFDN (MLL-AF6), t(6;11)(q27;q23), KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23), KMT2A::AFF1 oligomerises through the retained AFF1 CHD, putting the commonest fusion in the oligomerisation class, KMT2A::ELL (MLL-ELL), t(11;19)(q23;p13.1), KMT2A::EPS15 (MLL-AF1p), t(1;11)(p32;q23) — the infant-ALL cytoplasmic partner, KMT2A::GAS7 (MLL-GAS7), t(11;17)(q23;p13) — three patients, and the best mouse model in the partner class, KMT2A::MLLT1 (MLL-ENL), t(11;19)(q23;p13.3), KMT2A::MLLT10 (MLL-AF10), t(10;11)(p12;q23), KMT2A::MLLT11 (MLL-AF1q), t(1;11)(q21;q23) — 28 patients, and not one functional experiment, KMT2A::MLLT3 (MLL-AF9), t(9;11)(p21.3;q23.3), KMT2A::MLLT3 across 612 genotyped patients: myeloid at every age, but 248 of them have ALL, and 157 of those are infants, KMT2A::MLLT6 (MLL-AF17), t(11;17)(q23;q12-q21) — the bridge case: a leucine zipper on a DOT1L-complex subunit, KMT2A::MYO1F, t(11;19)(q23;p13.2) — recurrent in infant AML, and never functionally tested, KMT2A::SEPTIN11 (MLL-SEPT11) — the fusion that cytogenetically impersonates t(4;11), KMT2A::SEPTIN2 (MLL-SEPT2), t(2;11)(q37;q23) — the therapy-related septin, KMT2A::SEPTIN5 (MLL-SEPT5 / MLL-hCDCrel-1), t(11;22)(q23;q11.2), KMT2A::SEPTIN6 (MLL-SEPT6), t(X;11)(q24;q23) and its cryptic insertion variants, KMT2A::SEPTIN9 (MLL-SEPT9 / MLL-MSF), t(11;17)(q23;q25), KMT2A::USP2 is invisible to karyotype and often to FISH, so these patients are misclassified as fusion-negative, KMT2A::USP2, inv(11)(q23.3q23.3) - the minor-BCR fusion that keeps the PHD fingers, KMT2A::USP8, t(11;15)(q23;q21) - three patients, and the second instance of a deubiquitinase partner, KMT2A*: a menin-blind, LEDGF-blind, SET-competent KMT2A protein made from out-of-frame reciprocal alleles, KOPB-26 (CVCL_7972): a t(9;11) B-ALL line from a 13-month-old, and the model for 42% of this partner's patients that nobody uses, Ledger: every module the KMT2A half loses, with coordinates, how each was confirmed, and whether its loss has been shown to matter, MAML2 (mastermind-like 2) - the Notch co-activator that is a KMT2A partner in leukaemia and in thymoma, Menin inhibitors are prescribed on 'KMT2A-rearranged', a category that contains proteins as different as KMT2A::AFF1 and KMT2A::USP2, MLLT10 / AF10 — domain architecture and residue coordinates, MLLT11 / AF1q — a 90-residue protein with no chromatin domain and no oligomerisation module, KMT2A partner in t(1;11)(q21;q23), MLLT3 is the commonest partner in therapy-induced KMT2A leukaemia: 49 of 142, and 47 of those are t-AML, MRD as a trial endpoint in KMT2A-rearranged leukaemia: high negativity rates, and almost none of them say which assay, MRD by fusion transcript: fast, standardised, partner-limited - and structurally blind to KMT2A*, MRD by genomic breakpoint: the only assay in this disease that is fusion-specific by construction, MYO1F — unconventional myosin IF, a KMT2A partner with neither a transactivation domain nor a dimerisation domain, N-of-1 and n-of-few: the custom-therapy route, and what it actually costs, No junction-specific antibody exists for any KMT2A fusion - and synovial sarcoma shows exactly what one would buy, Non-elongation KMT2A partners considered and not written: what the searches actually returned, partner by partner, Only 4 of 43 open menin- or DOT1L-inhibitor trials admit infants under one year (9.3%), and only one (TINI-2) is infant-specific, though infants are about a third of the characterised KMT2A-rearranged population, Open ground: the questions in this graph that nobody in the landscape appears to be working on, Ordering the fusions developmentally — which stage of blood formation each one hijacks, and at what age the child presents, Put three descriptions of the same address on one hg38 axis - the exon-11 CTCF site, the intron-10/exon-11 functional cut point, and the region that breaks more in patients who got a KMT2A fusion - and find out whether they are one element, Repairing 85 defective citation blocks, and the finding that the queue's own numbers were wrong in three directions at once, Rolf Marschalek & Claus Meyer (DCAL, Goethe-University Frankfurt) — the world's KMT2A breakpoint dataset, Run in coordinates: the protective CTCF site and the patient break-prone window are ONE element, it is cohesin-bound, and the 'functional cut point' is 3.75 kb away - two of the graph's three exon-11s were the same exon and the third was not, Severability (contract law) — what survives when a clause is struck, and what survives a KMT2A break, Spliced and balanced KMT2A::MLLT1 do not automatically make the same oncoprotein - unless you restrict the comparison, which nobody has, Spliced KMT2A fusions join to partner exon 2 — with the per-partner counts, and a correction, Spliced KMT2A fusions: breaks upstream of the partner's exon 1, and the reciprocal-free natural experiment, Step 3: the G-banded karyotype and t(4;11)(q21;q23), Step 4: the split-signal FISH nucleus - one fusion, one green, one red, Step 5: molecular confirmation and naming the partner, t(11;19) is the largest named partner group in the revumenib registration trial - and the trial never resolves whether those patients have MLLT1 or ELL, t(9;11) is the reciprocal-POSITIVE arm: 2 of 612 patients are spliced, against 241 of 460 for t(11;19), The "second breakpoint cluster region" of KMT2A (Meyer 2019): the founding report of BCR2, not a third cluster, The anti-MLL-C ambiguity is not a t(4;11) problem - it has three sources, and one KMT2A fusion family is measurably cleaner than the rest, The deferred KMT2A partners: what the counts actually are, what was written, what was rejected, and three numbers the previous enumeration got wrong, The experiment: cross-tabulate MLLT1 breakpoint class against age, lineage and outcome in the Frankfurt archive, then confirm reciprocal status by RNA in whoever has it, The grading rule: confidence grades the claim, not the source - so one paper carrying several grades is correct, and only a three-step spread is worth reading, The infant breakpoint mutilates the reciprocal protein's first PHD finger - so 'the reciprocal product' is at least two different proteins, The KMT2A::MLLT1 chimeric protein: exactly what survives the join on each side, in residue numbers, The most faithful mouse models of t(11;19) are reciprocal-positive by design, and the commonest ones carry no reciprocal allele at all - and nobody has compared them, The MRD target a centre can run decides which infants are intensified, and the two targets disagree in the direction that matters, The partner-matched control arm is not 241 versus 219 - it is 153 versus 101, and in that subset the two groups make an identical fusion protein, The partner's deubiquitinase domain is what lets a PHD-retaining KMT2A fusion survive and transform, The protein nobody can attribute by antibody is the one mass spectrometry finds most easily, The reciprocal fusion (AFF1::KMT2A and friends): a second oncoprotein that opens chromatin for the first, The reciprocal MLLT1::KMT2A transcript was reported in the paper that discovered KMT2A, and nobody has gone back to it in thirty-four years, The YEATS asymmetry is breakage geography, not selection: the reader's fate is decided by where topoisomerase II cuts, before any leukaemia exists, USP2 (ubiquitin carboxyl-terminal hydrolase 2) - the ninth commonest KMT2A partner and the only one that is a deubiquitinase, USP8 (UBPY) - the second deubiquitinase KMT2A partner, three patients, same UCH logic, WDR5 — the partner that is not a partner: it binds the half of KMT2A the fusion throws away, What is a fusion gene?, What is actually conserved across KMT2A partner classes — forced self-association, with two documented exceptions that break the rule, Where KMT2A::MLLT3 sits in the nucleus: two papers, both overexpression, both from before 2005 - and the fusion carries no AF9 import signal, Where t(9;11) actually breaks inside MLLT3: 98.4% downstream of exon 4, and the two patients in 442 who kept the reader, Which partner, in which patient: KMT2A partner frequencies across six age-lineage strata, Who holds the data and samples we cannot generate ourselves — an access map, Who the 460 KMT2A::MLLT1 patients actually are: 88% lymphoblastic, 53% infants, and only 47 cases of AML in the whole series
501. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 36662616
     VGLL4 and MENIN function as TEAD1 corepressors to block pancreatic beta cell proliferation.

     Li F, Liu R, Negi V, Yang P, Lee J, Jagannathan R, et al. · Cell Reports 2023
     used by A second brake, unconnected to JunD: menin is a TEAD1 corepressor with VGLL4 in the beta cell
502. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37949879
     PRMT2 promotes HIV-1 latency by preventing nucleolar exit and phase separation of Tat into the Super Elongation Complex

     Jin J, et al. · Nature communications 2023
     used by A two-compartment switch for a SEC cargo: nucleolar retention versus AFF4-induced nucleoplasmic droplets, set by one methylated arginine, AFF4 — the textbook SEC scaffold that KMT2A::AFF1 cells need LESS than other leukemias
503. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36435883
     The ENL YEATS epigenetic reader domain critically links MLL-ENL to leukemic stem cell frequency in t(11;19) Leukemia.

     Hu H, Saha N, Yang Y, Ahmad E, et al. · Leukemia 2023
     used by ACER1 is on the list of in-frame reciprocal KMT2A partners - and ACER1 is the gene the 'reciprocal-negative' breakpoints fall next to, ATM phosphorylates ENL at conserved SQ sites and flips it from elongation to Polycomb repression - on sequence every KMT2A::MLLT1 fusion keeps, BCOR, not CBX8, is the AHD contact MLL-AF9 cannot lose - and the same two partners bind ENL far more tightly than AF9, DOT1L and H3K79 in KMT2A::MLLT1: a direct partner contact, mutually exclusive with the elongation complex, and the only fusion with a DOT1L-inhibitor complete remission, Every human t(11;19) KMT2A::MLLT1 cell line, with accessions fetched and read back - and not one of them is known to be reciprocal-negative, HB11;19 (CVCL_8227) keeps the YEATS domain and expresses both derivative transcripts - so it is the reciprocal-POSITIVE t(11;19) line, and there is no negative one, How general is subtraction across KMT2A fusions? Common enough to matter, too heterogeneous to be one thing, and mostly invisible to the way this project searches, Induction chemotherapy phospho-inactivates KMT2A fusions through PIKK sites the partner retains - and a DNA-PK or ATM inhibitor would block that, Is the drug target always in the retained half? An audit of the project's own framing, Is the YEATS asymmetry just intron geometry? Computed from hg38: the direction is explained, the magnitude is not, and both genes fail the same prediction, KMT2A::MLLT1 engages P-TEFb through one 66-residue surface: the ENL AHD, residues 494-559, and L550E breaks it, KMT2A::MLLT1 versus KMT2A::MLLT3: paralogous partners whose chromosomes break on opposite sides of the same domain, KOPN-8 (CVCL_1866): the field's default KMT2A::MLLT1 line, and its fusion protein has no YEATS domain, MLLT1 (ENL) refutes the YEATS parallel: the reader is retained in 84% of patients and is required for leukemogenesis, Phosphosite counts for the five 3' partners: the atlas beats UniProt 1.4-6.0x, and the retained/lost split is completely different for each partner, Restore the AF9 YEATS reader in cis to MLL-AF9, and read out the ENL patients who already did the experiment for us, SGC-iMLLT - the MLLT1/MLLT3 YEATS chemical probe, and the 2026 paper that put it into KMT2A::AFF1 in vivo with a healthy-HSPC comparison, Spliced and balanced KMT2A::MLLT1 do not automatically make the same oncoprotein - unless you restrict the comparison, which nobody has, Subtraction is a partner class, not a curiosity — and the class is defined by compartment, not by sequence, t(9;11) is the reciprocal-POSITIVE arm: 2 of 612 patients are spliced, against 241 of 460 for t(11;19), The 2x2 paralogue swap: separate 'is the reader there' from 'which backbone is it on', in one background with matched expression, The ENL YEATS acetyl-reader inside KMT2A::MLLT1: what it reads, what it does, and why both control arms carry it, The experiment: cross-tabulate MLLT1 breakpoint class against age, lineage and outcome in the Frankfurt archive, then confirm reciprocal status by RNA in whoever has it, The KMT2A::MLLT3 chimeric protein: what survives the join on each side, in residue numbers - and the four AF9 modules that do not, The most faithful mouse models of t(11;19) are reciprocal-positive by design, and the commonest ones carry no reciprocal allele at all - and nobody has compared them, The order in which the fusion's programme collapses is a property of the partner, not of KMT2A - so there is no single causal chain, The partner-matched control arm is not 241 versus 219 - it is 153 versus 101, and in that subset the two groups make an identical fusion protein, The transfer rule: which MLL-AF9 results can be carried into t(11;19) and t(4;11), and which are statements about a protein missing a reading module, The YEATS asymmetry is breakage geography, not selection: the reader's fate is decided by where topoisomerase II cuts, before any leukaemia exists, Where KMT2A::MLLT1 actually sits: chromatin occupancy is mapped, subnuclear localisation of the endogenous fusion has never been imaged, Where t(9;11) actually breaks inside MLLT3: 98.4% downstream of exon 4, and the two patients in 442 who kept the reader
504. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.reviewPMID 37295550
     The YEATS domain epigenetic reader proteins ENL and AF9 and their therapeutic value in leukemia.

     Hu H, Muntean AG · Experimental Hematology 124:15-21 2023
     used by Acetylation is a cycle, not a mark - and this graph holds one complete cycle, on a residue the fusion throws away, DNA-PKcs phosphorylates AF9 at S395 and releases it from the super elongation complex - the only AF9 regulatory element the fusion keeps, Four regulatory elements on AF9, and the fusion keeps exactly one - the phospho-switch that controls SEC binding, KAT2B / PCAF - named in an existing entry's own id and never written, and the only acetyltransferase in this graph whose substrate is a fusion partner protein, MLLT1 (ENL) refutes the YEATS parallel: the reader is retained in 84% of patients and is required for leukemogenesis, MLLT3 (AF9): the YEATS acetyl-lysine reader is discarded in ~92% of MLL-AF9 patients — same shape as PZP, but the causal test has never been run, Phosphosite counts for the five 3' partners: the atlas beats UniProt 1.4-6.0x, and the retained/lost split is completely different for each partner, Restore the AF9 YEATS reader in cis to MLL-AF9, and read out the ENL patients who already did the experiment for us, The AF9 acetylation arm: PCAF at K339, HDAC5 gated by CaMKII - a kinase-controlled switch the fusion throws away
505. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37740239
     Modelling acquired resistance to DOT1L inhibition exhibits the adaptive potential of KMT2A-rearranged acute lymphoblastic leukemia

     Schneider P, Crump NT, Arentsen-Peters STCJM, et al. · Experimental Hematology & Oncology 2023
     used by Adaptive, non-genetic resistance — the leukemia keeps the fusion and rewires how it is maintained, Buying an already-impaired asset — what diligence would you do, and what is the biological equivalent?, Hypothesis: prior therapy itself installs menin-inhibitor resistance, and the dose of prior therapy predicts it better than any mutation does, Myeloid-directed antigens (CD33, CD123) — the only immunotherapy axis that survives lineage switch, Pinometostat (EPZ-5676) — the DOT1L inhibitor, and the most instructive failure in this field, Thomas Milne (MRC WIMM, Oxford) — MLL-AF4 target biology, enhancer architecture and PROM1/CD133
506. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 37788669
     Epigenetic balance ensures mechanistic control of MLL amplification and rearrangement.

     Gray ZH, Chakraborty D, Duttweiler RR, Alekbaeva GD, Murphy SE, Chetal K, Ji F, Ferman BI, Honer MA, Wang Z, Myers C, Sun R, Kaniskan HU, Toma MM, Bondarenko EA, Santoro JN, Miranda C, Dillingham ME, Tang R, Gozani O, Jin J, Skorski T, Duy C, Lee H, Sadreyev RI, Whetstine JR · Cell 2023
     used by Adjudicated: CTCF does not do opposite things at KMT2A - it does one thing, and this graph's contradiction is an untested premise about whether a break becomes a rearrangement, Ask whether the childhood AML in the KDM3B-haploinsufficiency syndrome cohort carried a KMT2A rearrangement - the one human test this mechanism has, and it is a records request, At the KMT2A anchor itself, KDM3B loss does not raise H3K9me1 AND H3K9me2 - it raises me1 3.9-fold while me2 FALLS to 0.44x, an inversion of the mono-to-di ratio that the paper's abstract describes as a joint increase, Both arrows on KDM3B depletion are broad: H3K9me1 rises genome-wide AND CTCF falls at 84.6% of 12,443 anchors - the KMT2A anchor's 0.40x is the 3.6th percentile among strength-matched anchors, not a unique event, CTCF loss on KDM3B depletion is a graded property of anchor strength, not a set of targeted events: decile medians fall monotonically 0.78 to 0.62 across 12,443 RPE anchors, and if that gradient is biological then every strong anchor in the genome is a candidate instability site, CTCF/cohesin occupancy at the KMT2A exon-11 anchor is both the cause of the break and the chaperone of its correct repair - so losing it gives FEWER breaks and MORE rearrangements, EHMT2 / G9a - the H3K9me1/2 writer that sets whether the KMT2A LOCUS ITSELF rearranges, and whose loss delays MLL-AF9 AML in a supplementary figure nobody can find, Eleven hand-picked intervals are not a null: the CTCF loss on KDM3B depletion scales monotonically with baseline anchor strength (decile medians 0.78 to 0.62), so a strong anchor compared against gene bodies looks unique and compared against its own strength class is the 58th of 1,625, Gray 2023's own 'exon 11 CTCF site' in RPE cells, measured: centroid GRCh38 chr11:118,488,662-118,488,761, inside canonical exon 11 and 34 bp from the independently measured summit - the graph's CTCF adjudication is confirmed, not overturned, H3K9me1 - the only H3K9 state whose level at the KMT2A breakpoint cluster region has ever been measured, and it is LOW there until KDM3B is removed, H3K9me2 - named sixty times in this graph with no entry of its own, the mark that defines the lamina-associated domains the fusion's targets sit beside, and the only H3K9 methylation state ever measured at a KMT2A fusion's own binding sites, In patient-derived H3K27M glioma, baseline H3K9me3 over the 7,466 bp KMT2A breakpoint cluster core sits at the 7.8th and 28.5th percentile of 59,821 width-matched CTCF-anchor windows (0.56x and 0.90x the random-tile median) - the methyl-poor-BCR pattern this graph found in epithelium and in a blood line, now in a third lineage and for the trimethyl state, JDI-12 - published as a JMJD1C inhibitor that preferentially kills KMT2A-rearranged leukaemia and spares cord blood, then used as 'KDM3i' to CREATE KMT2A rearrangements in cord-blood progenitors, by two papers that do not cite each other, JMJD1C / KDM3C - named in three entries of this graph as one of the only loci that loses fusion occupancy under a menin inhibitor, ranked 23rd of 17,728 for KMT2A-selective dependency in this project's own scan, with the strongest published shRNA effect in SEM - and no entry until now, KDM3B - the H3K9me1/2 demethylase that sits on the KMT2A breakpoint cluster region and keeps it from rearranging, and the only leukaemia gene in this graph whose direction of effect flips between the myeloid and the lymphoid literature, Not one of the four studies in this dispute measured CTCF or cohesin occupancy in a human blood cell - so this beat read ENCODE instead, and the element is a STRONGER CTCF site in a B-lymphoblastoid line than in HCT116, with the summit at the same base, One demethylase family sits at both ends of this disease - KDM3B gates whether KMT2A rearranges, JMJD1C is what the resulting fusion needs to survive - and a single compound hits both, so its therapeutic index runs in opposite directions in the two cell populations it reaches, ONE GEO series can carry TWO different chrom tables: GSE210480's H3K9 bigWigs declare hg19 + exactly 100,000 bp but its CTCF bigWigs declare EXACTLY hg19 with no padding - so a build check run on one file does not license the rest of the series, Put three descriptions of the same address on one hg38 axis - the exon-11 CTCF site, the intron-10/exon-11 functional cut point, and the region that breaks more in patients who got a KMT2A fusion - and find out whether they are one element, Re-analyse the eight unreported H3K9me3 samples in GSE210480 at the KMT2A breakpoint cluster region - compute only, and it decides whether the rearrangement brake is mark-specific, Run in coordinates: the protective CTCF site and the patient break-prone window are ONE element, it is cohesin-bound, and the 'functional cut point' is 3.75 kb away - two of the graph's three exon-11s were the same exon and the third was not, RUN: the eight unreported H3K9me3 samples of GSE210480, read at the KMT2A CTCF element - H3K9me3 does not move where H3K9me1 moves 3.9-fold, and the me1/me2 positive controls passed, The anchor-matched ranking, run: the KMT2A exon-11 CTCF anchor is rank 58 of 1,625 anchors matched on baseline strength - the 3.6th percentile - and the matched MEDIAN anchor also falls to 0.63x, so 'CTCF falls only at the KMT2A anchor' is refuted while 'the KMT2A anchor loses more than most' survives weakly, The CTCF site in KMT2A exon 11 - a conserved insulator element sitting exactly on the functional cut point of the breakpoint cluster region, whose occupancy decides whether the locus rearranges, The decisive test that needs no new data: overlay the 12,443-anchor CTCF-loss ranking on the copy-number changes Gray 2023 reports, and ask whether the 280 anchors that lose CTCF as hard as KMT2A also amplify, The experiment the public data cannot supply: H3K9me1/2/3 and CTCF at the KMT2A exon-11 anchor in a cord-blood CD34+ progenitor, with and without KDM3B depletion, The H3K9me1/2-CTCF brake: a KDM3B-G9a balance keeps the KMT2A breakpoint cluster region methyl-poor and CTCF-bound, and losing either end makes the locus amplify and rearrange - in epithelium, in primary cord-blood progenitors and in mice, The H3K9me3 null that appears to exonerate prophylactic G9a inhibition was measured in retinal pigment epithelium, at 1 kb resolution, with n = 2 - and the warning it appears to lift lives in a leukaemic blast, The H3K9me3 writer reaches the KMT2A anchor only through CTCF and only after the break - which would make this graph's CTCF arm and its H3K9 arm one arm, with CTCF upstream, and would make every resting-state H3K9me3 measurement at that element the wrong assay, The KMT2A exon-11 anchor is not uniquely TARGETED by the KDM3B-G9a axis - it is unusually SENSITIVE to an H3K9me1 rise that happens almost everywhere, and the sensitivity is a property of the element, The KMT2A exon-11 CTCF anchor, placed in its population: baseline strength 4.92x (91.7th percentile of 12,443 RPE anchors), KDM3B-depletion ratio 0.396x, rank 58 of 1,625 strength-matched anchors - a strong, strongly-responding anchor at the edge of a continuum, not an outlier, The measurement that settles the CTCF dispute: degron-grade CTCF removal versus cohesin removal, with DNA breaks AND rearrangement outcome read out at the same 1 kb of KMT2A in the same cells, reported as rearrangements per break, The null the claim needed: the KMT2A BCR ranks 72 of 18,082 chromosome-11 bins for its H3K9me1 response - top 0.40% - while the same locus ranks 3,877th for H3K9me3 and 10,276th for H3K9me2, The off-target surface, measured rather than feared: KDM3B depletion moves CTCF occupancy at 84.6% of 12,443 RPE anchors and halves it at 1,436 - so an H3K9-axis drug given to prevent one rearrangement is remodelling loop architecture genome-wide, and preferentially at the strongest anchors, The one experiment that would separate the H3K9me1/2 rearrangement brake from H3K9me3 was run, deposited as eight public samples, and reported nowhere in the paper, The paper's four comparison loci, marks read against FISH calls: the H3K9 mark response agrees with the cytogenetic response at two loci and contradicts it at two - the mark is neither necessary nor sufficient, The resolution floor: every deposited H3K9 track in GSE210480 is 1,000 bp binned, so the 147 bp exon-11 question cannot be answered from the processed files - and the planned analysis that asked for 500 bp windows was asking for something that is not there, UNC0642 - the G9a/GLP chemical probe that abolished doxorubicin-induced Kmt2a copy gain in mice, and the one intervention in this beat that has been given to an animal, What is left after the missing arm was read: there is no H3K9me1, me2 or me3 measurement at the KMT2A breakpoint region in ANY haematopoietic cell, and the founding paper's own archive contains none because all 60 of its samples are epithelial, What the CTCF-protects paper actually cites: it names Gothe and Atkin in ONE direction-free sentence and declares the direction unresolved, and the two papers that ran the reciprocal experiment are absent from all 81 of its references
507. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37031220
     MOZ/ENL complex is a recruiting factor of leukemic AF10 fusion proteins.

     Komata Y, Kanai A, et al. · Nature communications 2023
     used by AF10/MLLT10 fusions drive aberrant self-renewal of non-stem progenitors — found only by opening the paper, CALM-AF10 reaches DOT1L through exactly the same OM-LZ interface as KMT2A::MLLT10 - the recruitment transfers, the addressing does not, The DOT1L-AF10 octamer - the second route to H3K79 methylation, required in MLL-AF10 and absent from KMT2A::AFF1
508. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 37306722
     ZNF384-Related Fusion Genes in Acute Lymphoblastic Leukemia.

     Zhu L, Bai W, Cheng Q, Fang J · Cancer Control 2023
     used by AKAP8 (AKAP95) - the only nuclear A-kinase anchoring protein, and the one that turned out to be required for MLL-rearranged leukaemia, AKAP8::ZNF384 - the same protein that MLL-rearranged leukaemia depends on is itself a rare B-ALL fusion partner, on the 5' side, donating its condensate-forming IDR, EWSR1::ZNF384 - the same EWSR1 exon 7 fragment that drives Ewing sarcoma, fused instead to a zinc-finger protein, in B-ALL, TAF15::ZNF384 - the FET-partner version, where the naming order in the literature is a trap and the founding experiment says the transactivation domain is not doing the work, ZNF384 - a C2H2 transcription factor that is the invariant 3' half of a whole B-ALL fusion subtype, including AKAP8::ZNF384
509. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36867579
     Diagnostic utility of whole genome sequencing in adults with B-other acute lymphoblastic leukemia.

     Leongamornlert D, Gutierrez-Abril J, Lee S, Barretta E, et al. · Blood Adv 2023
     used by AKAP8::ZNF384 - the same protein that MLL-rearranged leukaemia depends on is itself a rare B-ALL fusion partner, on the 5' side, donating its condensate-forming IDR, ZNF384 - a C2H2 transcription factor that is the invariant 3' half of a whole B-ALL fusion subtype, including AKAP8::ZNF384
510. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37742191
     ALKBH5 modulates hematopoietic stem and progenitor cell energy metabolism through m(6)A modification-mediated RNA stability control

     Gao Y, et al. · Cell Rep 2023
     used by ALKBH5 — the second m6A eraser: a cancer-stem-cell self-renewal role elsewhere, one incidental KMT2A record, and a flat dependency row
511. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36922593
     The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia

     Issa GC, Aldoss I, DiPersio J, Cuglievan B, Stone R, Arellano M, Thirman MJ, Patel MR, Dickens DS, Shenoy S, Shukla N, Kantarjian H, Armstrong SA, Perner F, Perry JA, Rosen G, Bagley RG, Meyers ML, Ordentlich P, Gu Y, Kumar V, Smith S, McGeehan GM, Stein EM · Nature 615:920-924 2023
     used by An occupancy readout returned background in every channel of the only drug-exposed patient sample it has been tried in - so a negative from such an assay cannot currently be told apart from an assay failure, Analysis (planned) — comparative druggability scan of every obligate fusion-partner interface in the atlas, CBFA2T3::GLIS2 supplies its own CAR-T antigen - FOLR1 came out of a list of fusion-specific genes in an isogenic human model. KMT2A-rearranged leukaemia is treated with a LINEAGE antigen it can abandon, or with one a drug has to create; nobody has built the fusion-specific surface list for KMT2A::AFF1., Differentiation syndrome is the one human pharmacodynamic readout KMT2A-rearranged leukaemia already shares with APL - and in APL it is a complication of a cure, while here it is a complication of a 30% response rate, Eytan Stein (MSKCC), Ghayas Issa (MD Anderson) and the clinical menin-inhibitor investigator network, How many children this affects, Hypothesis — the menin lesson generalises: every non-enzymatic fusion has an obligate partner interface that is more druggable than the fusion, Hypothesis: the paediatric gap is set by the population ratio, not by paediatric biology, KMT2A-rearranged acute leukemia across all ages: infants are 4% of it, Mechanism class 1 — chromatin and elongation hijack (KMT2A-r, NUP98-r), Model: predicting who responds to a menin inhibitor - no patient-level data is public, so this cannot be trained either, MRD as a trial endpoint in KMT2A-rearranged leukaemia: high negativity rates, and almost none of them say which assay, NUP98 fusions share the menin dependency (confirmed preclinically) — and the partner-supplied reader/writer module is not why, Revumenib (SNDX-5613, Revuforj) — first approved menin–KMT2A interface inhibitor, Scott Armstrong & Andrei Krivtsov (Dana-Farber / Boston Children's) — the group that turned menin dependency into a drug, Spike-in-normalised menin CUT&RUN with paired N- and C-terminal KMT2A antibodies in an infant KMT2A::AFF1 sample, on and off drug, in the same disease state, The compound in the only infant menin-inhibitor occupancy sample is revumenib, named in the abstract - and neither the dose nor the duration of exposure is recorded in the paper, the GEO record or the authors' repository, The platform argument's best evidence: one drug, two genotypes, one interface, Why PML::RARA became curable — and what KMT2A::AFF1 does not share with it
512. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 37099340
     Blinatumomab Added to Chemotherapy in Infant Lymphoblastic Leukemia

     van der Sluis IM, de Lorenzo P, Kotecha RS, et al. · New England Journal of Medicine 2023
     used by Analysis (runnable): fit the relapse hazard function in KMT2A-rearranged infant ALL and test whether the cohort is a mixture, Analysis (runnable): value a menin inhibitor as a short-duration instrument — cohort meta-regression plus a discrete-event model of remission months, Bayesian borrowing: how many infants a prior is worth, and when it lies, Blinatumomab in infant KMT2A-rearranged ALL — the largest single outcome gain in thirty years, CNS disease at diagnosis in infants: a real excess, measured by a procedure that partly creates it, External and historical controls: the design infant leukemia actually uses, Fever and infection: the reason most of these babies see a doctor, and the reason some of them die, How many children this affects, Hypothesis: KMT2A-rearranged infant ALL is two populations, not one — a mixture-cure model will fit better than proportional hazards, and combination therapy only needs to be given during the first year, Hypothesis: the survival benefit of menin inhibition is governed by the rate at which it delivers patients to a curative consolidation, not by its remission rate — and the field is measuring the wrong thing, Infant acute lymphoblastic leukaemia (ALL diagnosed under 1 year of age), Kinase/PI3K/RAS pathway activation — the only common co-lesion class in KMT2A-r leukemia, and it is mostly subclonal, Lineage switch as antigen escape from CD19-directed therapy in KMT2A-rearranged leukemia, Rob Pieters, Inge van der Sluis & the Interfant consortium (Princess Maxima Center, Utrecht) — the only global infant-ALL trial network, Term structure of risk — a steeply falling hazard curve is a statement about heterogeneity, not about time, The national scale: about 24 infants a year in England and Wales, about 12 in Australia, The near-silent genome of infant KMT2A-r ALL — 1.3 non-silent mutations, and why that is bad news as well as good, What 160 infants a year actually permits: the sample-size arithmetic, Which immune-evasion routes are actually documented in KMT2A-rearranged disease, and which are borrowed from AML and assumed - a ranked ledger with the bounded absences that define it
513. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38049829
     Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia

     Tubio-Santamaria N, ... Heidel FH · Molecular Cancer 2023
     used by Analysis: cross-validating the single-group non-menin KMT2A-fusion dependencies in one framework, Open ground: the questions in this graph that nobody in the landscape appears to be working on, The second ring — smaller KMT2A-fusion mechanism labs, and where the literature actually points
514. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 36635503
     Targeting Menin disrupts the KMT2A/B and polycomb balance to paradoxically activate bivalent genes.

     Sparbier CE, Gillespie A, Gomez J, Kumari N, Motazedian A, Chan KL, et al., Dawson MA · Nat Cell Biol 2023
     used by Another fusion family did the experiment this beat wants: in FUS::ERG and CBFA2T3::GLIS2 AML, MHC class I and II are absent at diagnosis, EZH2 drives it, and an EZH2 inhibitor restores presentation, Does the fusion's programme fall apart in the same order in KMT2A::AFF1 as in MLL::AF9? The chain's only ordering measurement, repeated on the index fusion, H3.3 - the graph's most-named epigenetic object with no entry, 325 mentions, and not one measurement in a KMT2A-rearranged cell, H3K4me3 - the mark KMT2A's own SET domain writes, that the fusion cannot write, that an interface in this graph already binds, and that switches PRC2 off, HLA-B - the class I heavy chain the bivalency screen was actually read out on, and the locus that presents the one KMT2A epitope this graph has a structure for, Hypothesis: a menin inhibitor must come BEFORE an antigen-directed immunotherapy, not with it or after it - and every published experiment has already assumed this without anyone testing it, IFNGR1 - the receptor the whole antigen-presentation mechanism runs through, and the one where low-dose interferon-gamma makes MLL-fusion leukaemia worse, In a cell with no fusion, a menin inhibitor is substantially a KMT2B drug, In a PCGF1-knockout clone the menin inhibitor still evicts and the vacated sites are still silenced, but LESS: H2AK119ub at the most-evicted quartile falls from 1.4450 to 1.1325 and from 1.0151 to 0.8842 in two replicate conventions, and H3K27me3 from 2.0007 to 1.0134 - so prediction 5's silencing clause is directionally right and quantitatively overstated, JAK1 - recruited and stabilised by AF10 fusions, and the kinase whose downstream STAT1 the class I effect of menin inhibition explicitly does not need, KMT2B (MLL2/MLL4) - the other protein menin binds, and the one this graph never wrote, Measure the menin-KMT2B affinity nobody has measured, and the four clinical inhibitors' IC50 against it, Menin holds KMT2A and KMT2B, and the graph has been written as if it held one, MHC class I is a bivalent gene set, and a menin inhibitor derepresses it - shown in K-562, SCLC and neuroblastoma, and measured on HLA-A in primary AML, but never once in a KMT2A-rearranged cell, MLL2 and MLL4 each name two different genes, and the ambiguity is in the papers, not in the databases, NLRC5 - the MHC class I transactivator, and the route by which interferon activates class I when KMT2A and KMT2B are both gone, PCGF1 — the PRC1.1 scaffold whose LOSS causes menin-inhibitor resistance, so it is a restraint on the leukaemia rather than a dependency of it, PRC1.1 is not both an effector and a resistance gene by coincidence: the two published readings are one activity measured from opposite ends, PRC2 - the complex, not the subunit, is the unit every experiment in this disease actually resolves, PRC2 is the fusion's repressive arm, recruited through menin, and the index disease's version of it runs to HDAC7, Tag endogenous KMT2B in an index-fusion line and measure what revumenib does to it - the experiment the reagents have blocked, The class I and class II arms of menin inhibition are different mechanisms - the class I effect was tested against viral mimicry and NF-kB and excluded both, The H3K27me3 absence this graph keeps asserting is narrower than stated: the measurement exists, in the genetic arm of the paper the graph cites for the phenocopy, The KMT2A-fusion causal chain: six links, one measured ordering, and two arms that are parallel rather than sequential, The missing measurement: is MHC class I bivalent, does a menin inhibitor raise it, and does raising it cost NK control - in a KMT2A-rearranged cell, for the first time, This cycle's word 'silenced' means two repressive marks up and one active mark down at 2 kb resolution - GSE260742 deposits no RNA-seq, no nascent transcription and no reporter for either NTvKO genotype, so whether the vacated sites stop being transcribed is unmeasured in the experiment that established they are marked for silencing, Trithorax against Polycomb at HOXA: the textbook antagonism, and the two ways this disease breaks it, What the Polycomb beat searched, what it counted as absent, what it read and rejected, and the two absences it got wrong before hand-back, When a family shares a complex, the result is family-selective, not member-selective - the protein version of this graph's inhibitor-class rule
515. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37611161
     Dissecting the role of SWI/SNF component ARID1B in steady-state hematopoiesis

     Madan V, Shyamsunder P, Dakle P, Woon TW, Han L, Cao Z, et al. · Blood Adv 2023
     used by ARID1B (BAF250b) - the cBAF paralogue whose deletion PROMOTES MLL-AF9 leukaemogenesis, which makes it the one gene in this beat whose published KMT2A-fusion result points the wrong way for a drug target
516. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37686014
     CRISPR-Cas9 Library Screening Identifies Novel Molecular Vulnerabilities in KMT2A-Rearranged Acute Lymphoblastic Leukemia.

     Schneider P, Wander P, Arentsen-Peters STCJM, Vrenken KS, Rockx-Brouwer D, Adriaanse FRS, Hoeve V, Paassen I, Drost J, Pieters R, Stam RW · International Journal of Molecular Sciences 2023
     used by ARID4B / SAP180 (Q4LE39) - the Sin3A-complex subunit that shares SIN3A's HDAC1-binding region, is in the MLL-fusion interactome, and is the second of only two epigenetic vulnerabilities a CRISPR screen found in KMT2A-rearranged ALL, MBD3 (O95983) - the methyl-CpG-binding subunit that does NOT bind methylated DNA, and a validated KMT2A::AFF1-selective CRISPR vulnerability that is absent from every column of the pan-fusion interactome, No experiment has ever ASKED whether MTA2, MBD3, GATAD2A or SIN3A binds a KMT2A fusion - four of them were nonetheless in the lysate of a seven-fusion pulldown, and the class of that absence is measured-not-reported, not never-measured, No histone-mark readout has ever been measured after perturbing ANY NuRD or Sin3 subunit in a KMT2A-rearranged cell - the two complexes whose entire job is acetylation have zero acetylation data in this disease, PROPOSED: a side-by-side CHD4 co-IP in a t(4;11) B-ALL line and a KMT2A-wildtype B-ALL line, probing one subunit from each NuRD module - the first experiment that would ask whether a KMT2A fusion sees the whole complex, SIN3A (Q96ST3) - the scaffold of the OTHER HDAC1/2 corepressor complex, a 5' fusion partner in infant B-ALL and in myelodysplasia, and present in three MLL-fusion AP-MS columns but not the index fusion's
517. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37832547
     DNA damage induces nuclear envelope rupture through ATR-mediated phosphorylation of lamin A/C.

     Kovacs MT, Vallette M, Wiertsema P, Dingli F, Loew D, Nader GPF, Piel M, Ceccaldi R · Mol Cell 2023
     used by ATR - the replication-stress kinase with the best preclinical case in this disease and the best published reason not to inhibit it
518. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 36868228
     DAXX adds a de novo H3.3K9me3 deposition pathway to the histone chaperone network.

     Carraro M, Hendriks IA, Hammond CM, et al. · Molecular Cell 2023
     used by ATRX - DAXX's partner and the other arm of H3.3 deposition; in this disease its only signal is in the four lymphoid cell lines, DAXX - the strongest of five selective dependencies among 254 unwritten interactors but it FAILS Bonferroni correction (p=0.0128, rank 4 of 254), and not one paper connects it to this disease
519. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36720973
     KDM6 demethylases integrate DNA repair gene regulation and loss of KDM6A sensitizes human acute myeloid leukemia to PARP and BCL2 inhibition

     See PubMed record PMID 36720973 for the full author list (not transcribed here) · Leukemia 2023
     used by Auditing the seven strikes before applying them: nine of ten decisions stand, four for different reasons than were given, and one clinical argument fails, KDM6B (JMJD3) - UTX's paralogue, which this graph has argued about for cycles without writing
520. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36380143
     Preclinical efficacy of azacitidine and venetoclax for infant KMT2A-rearranged acute lymphoblastic leukemia reveals a new therapeutic strategy.

     Cheung LC, Aya-Bonilla C, Cruickshank MN, et al. · Leukemia 2023
     used by Azacitidine - the one hypomethylating agent actually given to infants with KMT2A-rearranged ALL: safe, demonstrably demethylating, and it did not change survival, COG AALL15P1 — azacitidine epigenetic priming in infant KMT2A-rearranged ALL: on-target, well tolerated, no survival effect, Decitabine - degrades DNMT1, and in ALL cells it degrades KMT2A too: the hypomethylating agent with two mechanisms and a menin-inhibitor combination already in the clinic, Decitabine degrades DNMT1 - and in ALL cells the same treatment lowers KMT2A protein, with the shared CXXC-family DNA-binding module offered as the reason, Decitabine's target is a pan-essential gene, and KMT2A-rearranged lines depend on it LESS than other leukaemia lines - rank 16,949 of 17,728, The 'infant ALL' PDX panel with four KMT2A::AFF1 models — one of which the full text calls adult, Venetoclax in KMT2A-rearranged leukemia — the apoptotic partner every other drug needs
521. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 37353482
     Molecular mechanism of phosphopeptide neoantigen immunogenicity.

     Patskovsky Y, Natarajan A, Patskovska L, Nyovanie S, Joshi B, Morin B, et al. · Nat Commun 2023
     used by B2M (beta-2 microglobulin) - the invariant light chain every MHC class I molecule needs, the classic class I escape route, and a gene this disease's literature has never once named, HLA-B - the class I heavy chain the bivalency screen was actually read out on, and the locus that presents the one KMT2A epitope this graph has a structure for, KMT2A 747-755 on HLA-B*07:02: a phosphoneoantigen from the half of KMT2A every fusion keeps, with seven crystal structures and a cognate TCR
522. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 37679565
     CRISPR-ChIP reveals selective regulation of H3K79me2 by Menin in MLL leukemia.

     Gilan O, Talarmain L, Bell CC, et al. · Nat Struct Mol Biol 2023
     used by Blocking where DOT1L binds instead of what it does - the modality that removes the mark only at fusion targets, CALM-AF10 was meant to separate the menin axis from the HOXA programme - and the indirect evidence has now turned against separability, because KMT2A-free HOXA lesions keep proving menin-DEPENDENT, H3K79me2 - the di-methyl state the leukaemia actually runs on, and the one menin turns out to govern only half of, Import class 3: the DOT1L-AF10 coiled-coil axis, an MLLT10 mechanism with no counterpart in the index fusion, KMT2A::AFF1 has no mapped interface to DOT1L: it lacks both structurally defined recruitment modules, and the one complex-level route claimed for it is contested by reconstitution, Measure all three H3K79 states on a real scale, across a dose series and after a menin inhibitor - the measurement this whole field has been doing by proxy, Menin inhibitors should leave half the H3K79 methylation standing - and if they do not, the menin-interface model is wrong somewhere, PICALM::MLLT10 (CALM-AF10), t(10;11)(p13;q14) - the DOT1L-dependent HOXA fusion that contains no KMT2A, The CRISPR-ChIP H3K79 partition is a mouse MLL-AF9 result: resolved from GEO after the full text proved unreachable, The DOT1L-AF10 octamer - the second route to H3K79 methylation, required in MLL-AF10 and absent from KMT2A::AFF1, The menin/H3K79 partition this graph leans on was measured in MURINE MLL-AF9 - resolved from GEO, because the abstract does not say, What this beat read and did not use: bounded absences, bounded rejections and one bounded unreadable, When a paper will not say what it was done in, ask its data: resolving an unstated experimental system from GEO
523. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 36264143
     A Molecular Switch between Mammalian MLL Complexes Dictates Response to Menin-MLL Inhibition.

     Soto-Feliciano YM, Sánchez-Rivera FJ, Perner F, et al. · Cancer Discov 2023
     used by Bounded absence: no published study has tested whether a KMT2A fusion GAINS chromatin sites under a menin inhibitor - and the same pipelines found gains for two other proteins when they looked, Bounded failure: 'menin inhibitor-resistant cells' is a drug entry's central claim and neither the paper nor any repository defines it, Census of every published chromatin-occupancy measurement made under a menin inhibitor: eight datasets, every one TSS-anchored, every one tabulating losses only, Hypothesis: menin inhibition does not clear the fusion from chromatin but redistributes it onto the four fifths of the unmethylated CpG address it normally ignores, Hypothesis: the menin inhibitor's effect is inactivation in place, not eviction - the fusion keeps most of its sites and loses its output, KMT2A-rearranged or NPM1-mutant? Both, in separate arms: WT-MA9 mouse, MOLM13, OCI-AML3, and two patients on AUGMENT-101, Menin inhibition is a reshuffle, not a subtraction: four proteins are documented to GAIN chromatin or persist under the drug, and none of them is the fusion, The MLL3/4-UTX switch fails to throw — menin inhibition kills by turning something ON, and cells that cannot turn it on survive
524. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     GSE225028 (SU-DIPG13, SU-DIPG36 CUT&RUN) and GSE139196 (MCF-7 ChIP-seq +/- estradiol) per-sample SOFT records

     Xin DE et al.; Yang F et al. · NCBI GEO 2023
     used by Bounded with every archive and every route named: after both public SUV39H1 deposits were read this cycle, there is still NO SUV39H1 occupancy measurement in any haematopoietic cell, any KMT2A-rearranged cell, or any damage state - in ENCODE (three routes, zero), ChIP-Atlas (one deposit, MCF-7 only) or GEO (two deposits, glioma and breast), In patient-derived H3K27M glioma, baseline H3K9me3 over the 7,466 bp KMT2A breakpoint cluster core sits at the 7.8th and 28.5th percentile of 59,821 width-matched CTCF-anchor windows (0.56x and 0.90x the random-tile median) - the methyl-poor-BCR pattern this graph found in epithelium and in a blood line, now in a third lineage and for the trimethyl state, Read at last, against a pre-registered class-matched null: in SU-DIPG13 and SU-DIPG36 the SUV39H1 CUT&RUN mean at the KMT2A exon-11 CTCF anchor is 0.0000 and 1.6660 - the first an EXPLICIT zero record, not missing data - and no one of the seven KMT2A intervals in either line exceeds 1.21x the genome-wide random-tile mean. The pre-registered NEGATIVE prior held., The H3K9me3 this graph argues about at the KMT2A exon-11 anchor is not deposited by SUV39H1: in SU-DIPG13 the mark sits at the 57.8th percentile of class-matched CTCF anchors while the writer reads an EXPLICIT ZERO in the same nuclei, and genome-wide the two barely track each other (Spearman 0.148, 0.078), The one experiment that would close the SUV39H1 arm of this graph's H3K9 argument: CST #8729S CUT&RUN in a CD34+ progenitor and in SEM or RS4;11, with an IgG arm and a SUV39H1-degron arm that neither existing deposit has - because after this cycle the enzyme has been measured in exactly two human cell types and neither is a blood cell, The rarest thing in the deposit, measured: across 59,821 CTCF anchors in the SAME nuclei, SUV39H1 occupancy and H3K9me3 correlate at Spearman 0.148 and 0.078 - and a quarter to two-fifths of the enzyme's own strongest sites carry no more of its mark than the median anchor
525. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36690674
     Structural mechanism of BRD4-NUT and p300 bipartite interaction in propagating aberrant gene transcription in chromatin in NUT carcinoma

     Yu D, Liang Y, Kim C, et al. · Nature Communications 2023
     used by BRD9::NUTM1, t(5;15)(p15.33;q14) - one fusion is enough to make infant B-ALL in a mouse, and it is the one that behaves best in a child, NUTM1 (NUT) - a testis-restricted, fully disordered protein that writes no mark and instead switches ON a writer, and the 3' partner of the KMT2A-wild-type infant B-ALL with the opposite prognosis
526. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.news
     FDORA Changes to the FDA Accelerated Approval Program

     Cooley LLP · Cooley client insight 2023
     used by Breakthrough therapy and accelerated approval: the menin field took the fast review and declined the shortcut
527. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37880389
     Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients.

     Yuda J, Will C, Phillips DC, ..., Souers AJ · Commun Med (Lond) 2023
     used by Cardiac troponin release on MCL-1 inhibition - reported for two structurally distinct compounds and described by one developer as a likely CLASS effect, which makes it an essential-function ceiling rather than a chemistry problem, Cardiomyocyte - the non-haematopoietic cell that two of this graph's drug targets are required in, which makes it the graph's clearest bystander-organ liability
528. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37553297
     Palbociclib in combination with chemotherapy in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia and lymphoma: A Children's Oncology Group study (AINV18P1)

     Raetz EA, Teachey DT, Minard C, Liu X, Norris RE, Denic KZ, Reid J, Evensen NA, Gore L, Fox E, Loh ML, Weigel BJ, Carroll WL · Pediatric Blood & Cancer 70:e30609 2023
     used by CCND3 (cyclin D3) — the scan's rank-4 hit, and the only one of the four with a drug class already in children, CDK4/6 inhibition in KMT2A-rearranged leukemia — the class was already tried, and the trial never reported, COG AINV18P1 (NCT03792256) — palbociclib is deliverable in children with relapsed ALL, at 50 mg/m² for 21 days
529. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37311511
     Leukapheresis and Tisagenlecleucel Manufacturing Outcomes in Patients Age <3 Years with Relapsed/Refractory Acute Lymphoblastic Leukemia

     Fong D, Tiwari R, Acker C, Clough L, Willert J · Transplantation and Cellular Therapy 2023
     used by CD19 CAR-T in infants with KMT2A-rearranged ALL — it works, it is manufacturable, and it does not hold
530. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 35950535
     Potent preclinical activity of FLT3-directed chimeric antigen receptor T-cell immunotherapy against FLT3-mutant acute myeloid leukemia and KMT2A-rearranged acute lymphoblastic leukemia

     Niswander LM, Graff ZT, Chien CD, et al. · Haematologica 2023
     used by CD19 CAR-T in infants with KMT2A-rearranged ALL — it works, it is manufacturable, and it does not hold, Lineage switch as antigen escape from CD19-directed therapy in KMT2A-rearranged leukemia, Myeloid-directed antigens (CD33, CD123) — the only immunotherapy axis that survives lineage switch
531. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.reviewPMID 36979800
     Updates in KMT2A Gene Rearrangement in Pediatric Acute Lymphoblastic Leukemia.

     Gorecki M, ..., Lejman M · Biomedicines 2023
     used by CD33 (SIGLEC3) - the aberrant myeloid antigen on a B-lineage blast, and the one antibody-drug-conjugate target with a positive randomised result in KMT2A-rearranged disease, MME / CD10 (CALLA) - the marker this disease is defined by NOT having, and the promoter is methylated shut rather than simply not yet switched on, Step 1: the blood count and the blood film, Step 2: flow cytometry and the CD10-negative pro-B fingerprint
532. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 36736154
     Discovery of novel and bioavailable histone deacetylases and cyclin-dependent kinases dual inhibitor to impair the stemness of leukemia cells.

     Liu Y, Wei Y, Wang X, Ma L, Li X, Sun Y, Wu Y, Zhang L, Wang J, Li M, Zhang K, Wei M, et al · Eur J Med Chem 2023
     used by CDK13 - rank 171 of 17,728, equally deep in both lineage halves, and essentially unstudied in leukaemia, Knock down CDK13 and CDK12 side by side in lineage-matched KMT2A and non-KMT2A lines, and ask whether the DepMap signal is real
533. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37205848
     Repression of TRIM13 by chromatin assembly factor CHAF1B is critical for AML development.

     Dean ST, Ishikawa C, Zhu X, et al. · Blood Advances 2023
     used by CHAF1B (CAF-1 p60) - the one histone chaperone in this beat with a real leukaemia literature, and a mouse experiment that contradicts DepMap's verdict on its druggability
534. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36849955
     Synergistic effect of HDAC inhibitor Chidamide with Cladribine on cell cycle arrest and apoptosis by targeting HDAC2/c-Myc/RCC1 axis in acute myeloid leukemia.

     Gu S, Hou Y, Dovat K, Dovat S, Song C, Ge Z · Experimental Hematology & Oncology 12(1):23 2023
     used by Chidamide (tucidinostat) - the HDAC inhibitor in both of this graph's menin-inhibitor combination papers, and the only one paired with a menin inhibitor in the lymphoid index disease, HDAC2 - the buffering half of the class I pair, and the one class I enzyme a drug result in acute leukaemia has actually been pinned to, in AML rather than in a KMT2A fusion
535. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37802054
     Cooperative CAR targeting to selectively eliminate AML and minimize escape.

     Haubner S, Mansilla-Soto J, Nataraj S, Kogel F, Chang Q, de Stanchina E, et al. · Cancer Cell 2023
     used by CLEC12A (CD371, CLL-1, MICL) - the leukaemic-stem-cell antigen whose therapeutic rationale rests on an absence, and which menin inhibition appears to induce, Risk: CLEC12A-directed therapy ablates normal granulocytes and disables an inhibitory brake on NET formation - the toxicity is mature-myeloid, not stem-cell
536. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 37626123
     MLL-AF4 cooperates with PAF1 and FACT to drive high-density enhancer interactions in leukemia

     Crump NT, ... Milne TA · Nature Communications 2023
     used by Collaborate or compete: an honest matrix, including where the lab would be duplicating a better-resourced effort, Counted absences keyed on a complex subunit miss the papers that name only the complex - demonstrated on our own SSRP1 entry, which declared no KMT2A paper about FACT while this graph cites one about the index fusion in four other entries, Enhancer usage in KMT2A-rearranged leukemia — occupancy and amplification, not hijacking, and not super-enhancers, H3K27ac - named in 40 entries with no entry of its own, and the strongest KMT2A::AFF1 measurement of it is invisible to every abstract search, PAF1 is annotated as punctate everywhere in the nucleus EXCEPT the nucleolus - and a 2024 proximity map puts it in the nucleolus, SSRP1 - the small FACT subunit, and the only protein in this beat that binds a confirmed KMT2A-fusion interactor directly (LEDGF/p75, via HMG box to PWWP), Thomas Milne (MRC WIMM, Oxford) — MLL-AF4 target biology, enhancer architecture and PROM1/CD133, Transcription–replication conflict as the candidate reason KMT2A-rearranged cells need the Fanconi pathway — a chain with two measured links and three inferred ones
537. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37474833
     Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy

     Coorens THH, Behjati S, et al. · Nature Cancer 2023
     used by Competitive release and adaptive therapy — what ecology says happens when you remove the dominant species, Experiment: go back to the diagnostic sample and look for the myeloid clone before it existed, Hypothesis: the myeloid clone that appears after CD19-directed therapy was already there at diagnosis, and its abundance is a pre-treatment biomarker, Myeloid-primed blasts are already present at diagnosis of KMT2A-rearranged B-ALL and expand under immunotherapy — the single-cell demonstration this graph recorded as not existing
538. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     CRISPR-ChIP to identify mechanisms of chromatin regulation [CRISPR-ChIP] (GSE192544)

     Gilan O, Dawson MA, et al. (GEO submitters) · NCBI Gene Expression Omnibus 2023
     used by Corrections owed to other beats: nine entries whose stated provenance is now resolvable, and one unflagged import, Import class 4: human myeloid cell lines standing in for infant B-lymphoid disease, The CRISPR-ChIP H3K79 partition is a mouse MLL-AF9 result: resolved from GEO after the full text proved unreachable, The unstated-system worklist: 26 sources carry a caveat of this class, 18 now resolve, and 13 of 16 new resolutions are imports
539. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     CRISPR-ChIP to identify mechanisms of chromatin regulation [ChIP-seq] (GSE192555)

     Gilan O, Dawson MA, et al. (GEO submitters) · NCBI Gene Expression Omnibus 2023
     used by Corrections owed to other beats: nine entries whose stated provenance is now resolvable, and one unflagged import, Repeat the H3K79 partition in a human KMT2A::AFF1 line: menin inhibition and MLLT10 knockout, side by side with a KMT2A::MLLT3 line, The CRISPR-ChIP H3K79 partition is a mouse MLL-AF9 result: resolved from GEO after the full text proved unreachable, What could refute the menin-interface bet, restated after the provenance audit: three tests, none of which is about menin binding, When a paper will not say what it was done in, ask its data: resolving an unstated experimental system from GEO
540. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38016475
     CPT1A induction following epigenetic perturbation promotes MAVS palmitoylation and activation to potentiate antitumor immunity.

     Zhang G, Jiang P, Tang W et al · Molecular Cell 2023
     used by CPT1A - the outer-mitochondrial-membrane fatty-acid gatekeeper that is also a lysine succinyltransferase, fused to KMT2A exon 3 in the one case that is tether WITHOUT address
541. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38026791
     CK2beta Regulates Hematopoietic Stem Cell Biology and Erythropoiesis.

     Quotti Tubi L, Canovas Nunes S, Mandato E, Pizzi M, Vitulo N, et al. · HemaSphere 2023
     used by CSNK2B / CK2beta (P67870) - the regulatory subunit of casein kinase 2, in the pan-MLL-fusion core, with no CSNK2B-and-KMT2A literature at all
542. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37259259
     Minimal residual disease predicts outcomes in KMT2A-rearranged but not KMT2A-germline infant acute lymphoblastic leukemia: Report from Children's Oncology Group study AALL0631.

     Faulk KE, Kairalla JA, Dreyer ZE, et al. · Pediatr Blood Cancer 2023
     used by ctDNA MRD under a menin inhibitor: blood flow diverges from blood DNA, because the disease is in the spleen and marrow, Flow-cytometric MRD: the fastest readout, and the one a lineage switch walks straight out of, Which MRD timepoint drives which decision in infant ALL, and how good the evidence for each is
543. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38053201
     Repressing HIF-1alpha-induced HDAC9 contributes to the synergistic effect of venetoclax and MENIN inhibitor in KMT2Ar AML

     Ling Q, Zhou Y, Qian Y, et al. · Biomark Res 2023
     used by CXCR4 function in KMT2A-rearranged blasts is an output of the fusion's own HOXA/MEIS1 program, so a menin inhibitor should switch off the niche axis without a CXCR4 antagonist, HDAC9 - the only HDAC with a KMT2A-rearrangement expression signature across 211 paediatric patients, and it is high, prognostic, and independent of partner and lineage, Hypothesis: treatment-remodelled niche, not niche-imposed dormancy, is what residual KMT2A-rearranged disease exploits, Niche-mediated chemoprotection in KMT2A-rearranged leukaemia — real for cytarabine, unsupported for menin inhibitors, and the one hypoxia experiment points the other way, Nobody has reported what a menin inhibitor does to CXCR4: zero papers name menin and CXCR4 together, and the RNA-seq that would answer it is already public, Planned: read CXCR4 and SYTL1 out of the menin-inhibitor transcriptomes that are already public, in the same contrast that shows HOXA9 and MEIS1 falling, Systematic enumeration of menin-inhibitor resistance mechanisms: seven entries written, thirteen candidates rejected with reasons, The hypoxic, glycolytic state — the one state that appears independently in leukaemia-initiating cells, in measurable residual disease, and in KMT2A-rearranged B-ALL as a class, The marrow oxygen gradient — low everywhere, lowest at the sinusoids, and in this leukaemia low oxygen helps the drug rather than the cell, The perivascular and sinusoidal niche — where the functional evidence actually sits, and where the marrow is genuinely hypoxic
544. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 37165190
     Structural basis of catalytic activation in human splicing.

     Schmitzová J, Cretu C, Dienemann C, Urlaub H, Pena V · Nature 2023
     used by DHX16 / hPRP2 (O60231) - the spliceosomal catalytic-activation helicase, pan-MLL-fusion, and one of only two in the 42 whose index-fusion p-value exceeds 0.05, PPIL4 - a spliceosomal cyclophilin whose BioID neighbourhood is the widest overlap with this graph's subject matter of any bait
545. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 35600388
     Case Report: First Report of T-Cell Large Granular Lymphocytic Leukemia With NPL-DHX9 Gene Fusion Successfully Treated With Cladribine: Clinical Experience and Literature Review.

     Hu N, et al. · Frontiers in Oncology 2023
     used by DHX9 / RNA helicase A (Q08211) - the other TDRD3 effector, and it is itself the 3' partner of a leukaemia fusion
546. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37615563
     Multivalency of nucleosome recognition by LEDGF.

     Koutná E, Lux V, et al. · Nucleic Acids Res 2023
     used by Does the fusion need the PWWP arm? An artificial CXXC + H3K36me2-reader + AF4-interaction protein substitutes for a whole MLL fusion - but LEDGF itself is not required for the fusion to reach chromatin, Phase-2 dossier: the LEDGF/PSIP1 IBD - the best therapeutic index in the interactome, a solved structure, two hotspot residues, and three compounds in the world
547. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37246732
     Insertion of the CXXC domain of KMT2A into YAP1: An unusual mechanism behind the formation of a chimeric oncogenic protein.

     Teku G, Nilsson J, Magnusson L, et al. · Genes Chromosomes Cancer 2023
     used by Does the sarcoma fusion bind menin? One co-immunoprecipitation with the right control settles six years of the question, Nobody has ever asked whether a KMT2A-rearranged sarcoma needs menin: zero records, and the reason is that no model exists, YAP1::KMT2A::YAP1 (YKY) - an insertional KMT2A rearrangement that keeps the CXXC zinc finger and throws the menin-binding exon away
548. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37759327
     Nucleophosmin 1 cooperates with the methyltransferase DOT1L to preserve peri-nucleolar heterochromatin organization by regulating H3K27me3 levels and DNA repeats expression.

     Izzo A, Akol I, Villarreal A, Lebel S, Garcia-Miralles M, Cheffer A, Bovio P, Heidrich S, Vogel T · Epigenetics Chromatin 2023
     used by DOT1L's localization record is a mouse kidney paper wearing a human label - and the one image of it in a leukaemia cell is a supporting figure a title search cannot see
549. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 37002435
     Zebrafish ELL-associated factors Eaf1/2 modulate erythropoiesis via regulating gata1a expression and WNT signaling to facilitate hypoxia tolerance.

     Liu W, Lin S, Li L, Tai Z, Liu JX · Cell Regen 2023
     used by EAF1 — the interactor with an actual subnuclear phenotype: an MLL fusion evicts it from Cajal bodies, and the bodies themselves fall apart, Erythroid progenitor - the committed red-cell precursor, distinct from the bipotent MEP that two entries had to borrow, and the compartment that pays for any haem-pathway or fetal-globin intervention
550. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37036970
     Interrogating bromodomain inhibitor resistance in KMT2A-rearranged leukemia through combinatorial CRISPR screens.

     Wright S, Hu J, et al. · Proc Natl Acad Sci U S A 2023
     used by Eleven immortalised lines passaged for decades: the competing explanation this beat could not close, Measure replication stress directly in KMT2A-rearranged cells instead of inferring it from a dependency ranking
551. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36763002
     In Vivo Screening Unveils Pervasive RNA-Binding Protein Dependencies in Leukemic Stem Cells and Identifies ELAVL1 as a Therapeutic Target.

     Vujovic A, de Rooij L, et al. · Blood Cancer Discov 2023
     used by Eleven immortalised lines passaged for decades: the competing explanation this beat could not close
552. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37102302
     TP53 and RB1 alterations characterize poor prognostic subgroups in pediatric acute myeloid leukemia.

     Hara Y, Shiba N, Yoshida K, Yamato G, Kaburagi T, Shiraishi Y, et al. · Genes Chromosomes Cancer 2023
     used by ELF1 - a direct transcriptional target of MLL fusion proteins and HOXA9 that is ALSO a BioID neighbour of KMT2A, and that is focally deleted in paediatric AML without a KMT2A rearrangement
553. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36843114
     Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes.

     Casado P, et al. · Signal Transduct Target Ther 2023
     used by ELL S309 is the most frequently observed phosphosite across public datasets - and it is a proline-directed site with no kinase, not an ATM site, KMT2A-rearranged AML is two diseases on the phosphorylation layer, and DOT1L phosphorylation is one of the things that separates them, MLLT10/AF10: twenty observed phosphosites, twelve PIKK motifs, and not one kinase-site relation in the literature - a bounded absence
554. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 36617428
     Cryo-EM structure of the fully assembled Elongator complex.

     Jaciuk M, Scherf D, et al. · Nucleic Acids Res 2023
     used by ELP5 (DERP6) - the bridge that joins ELP3 to ELP4, the most essential Elongator subunit in DepMap, and a gene whose cytoplasmic call rests on an overexpression experiment, ELP6 (TMEM103/C3orf75) - an Elongator subunit named after a membrane protein it is not, whose entire localisation record comes from a Drosophila paper its own symbol cannot retrieve
555. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37494611
     Establishment of a t(11;19), KMT2A Rearranged B-ALL Cell Line for Preclinical Evaluation and Novel Therapeutic Discovery

     Sharma R, Incoronato A, Zhang C, et al. · PubMed record 2023
     used by Enumeration for the index-fusion model beat: what was searched, found, rejected and could not be read
556. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37969120
     Prognostic importance of the fusion partners and measurable residual disease in patients with acute myeloid leukemia who harbor 11q23/KMT2A alterations.

     Mrózek K · Transl Pediatr 2023
     used by Enumeration for the partner-outcome beat: what was searched, what was used, what was rejected, what could not be read
557. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 38026790
     Integration of Transcriptomic Features to Improve Prognosis Prediction of Pediatric Acute Myeloid Leukemia With KMT2A Rearrangement.

     Li J, Zong S, et al. · Hemasphere 2023
     used by Enumeration for the partner-outcome beat: what was searched, what was used, what was rejected, what could not be read
558. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36095844
     EVI1 drives leukemogenesis through aberrant ERG activation

     Schmoellerl J, Barbosa IAM, Minnich M, Andersch F, Smeenk L, Havermans M, Eder T, Neumann T, et al. · Blood 141:453-466 2023
     used by ERG - a heptad stem-cell transcription factor whose 15 mentions in this graph are mostly about OTHER diseases, and whose best-established role in B-ALL is loss of function, not cooperation, MECOM (EVI1) - a cell-of-origin memory that MLL-AF9 maintains but cannot install, present in about 43% of MLL-rearranged AML and marking the chemoresistant half
559. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37738561
     HEXIM1 is an essential transcription regulator during human erythropoiesis.

     Lv X, Murphy K, Murphy Z, Getman M, Rahman N, Nakamura Y, et al., Steiner LA · Blood 2023
     used by Erythroid progenitor - the committed red-cell precursor, distinct from the bipotent MEP that two entries had to borrow, and the compartment that pays for any haem-pathway or fetal-globin intervention, HEXIM1 - the brake pad, the only part of the reservoir anyone has deliberately raised in a KMT2A-rearranged cell, and the result was that the leukaemia grew less
560. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36959690
     VIM::KMT2A-rearranged sarcomas: A report of two new cases confirming an entity with distinct histologic features.

     Almohsen SS, Griffin AM, Dickson BC, et al. · Genes Chromosomes Cancer 2023
     used by Every published KMT2A partner in sarcoma, counted - plus the papers this beat read and did not use, so the next beat does not repeat the search without the decisions, KMT2A-rearranged soft tissue sarcoma - the same gene as infant B-ALL, in a young adult's leg, as a solid tumour, VIM / vimentin (P08670) - a pan-MLL-fusion prey with a clean negative control, and separately a genuine KMT2A rearrangement partner in sarcoma, which are two different facts, VIM::KMT2A - the one KMT2A rearrangement that keeps the SET domain and still throws away the menin-binding exon
561. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37713130
     KMT2A-rearranged sarcoma with unusual fusion gene CBX6::KMT2A::PYGO1.

     Nakamura H, Kukita Y, Wakamatsu T, et al. · Virchows Arch 2023
     used by Every published KMT2A partner in sarcoma, counted - plus the papers this beat read and did not use, so the next beat does not repeat the search without the decisions, In leukaemia KMT2A gives the front of the protein; in sarcoma it gives the back. Every consequence follows from that., KMT2A-rearranged soft tissue sarcoma - the same gene as infant B-ALL, in a young adult's leg, as a solid tumour
562. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 36453131
     IMPDH inhibition activates TLR-VCAM1 pathway and suppresses the development of MLL-fusion leukemia.

     Liu X, ..., Goyama S · EMBO Molecular Medicine 2023
     used by Every upstream NF-kB component this beat enumerated, with its query, its count, and why it did or did not get an entry, IL-1/IRAK1/4 — the receptor-proximal input the MLL screen actually pointed at, with an Il1r1 knockout in MLL-AF9 mice and an inhibitor that spares normal stem cells, IMPDH2 - the rate-limiting guanine-nucleotide enzyme whose inhibition lowers LEDGF and menin protein and dismantles the MLL-fusion complex itself, Repurposing approved IMPDH inhibitors (mycophenolate, mizoribine, ribavirin) in KMT2A-rearranged leukaemia - cheap, mechanistically attractive, and asking an immunosuppressant of a neutropenic infant, The innate-immune-rewired state — LAMP-5 is a direct fusion target that routes signalling away from interferon and toward NF-kB, and the cell depends on that routing, VCAM1 - the stromal counter-receptor for VLA-4, and in MLL-fusion AML its UPREGULATION is anti-leukaemic, which is the opposite of the expected sign
563. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37370721
     Bone Marrow Microenvironment-Induced Chemoprotection in KMT2A Rearranged Pediatric AML Is Overcome by Azacitidine-Panobinostat Combination

     Lehner KM, Gopalakrishnapillai A, Kolb EA, Barwe SP · Cancers (Basel) 2023
     used by Experiment: does marrow stroma protect KMT2A-rearranged cells from a menin inhibitor? Nobody has run the week-long experiment that would say, Niche-mediated chemoprotection in KMT2A-rearranged leukaemia — real for cytarabine, unsupported for menin inhibitors, and the one hypoxia experiment points the other way
564. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 35482927
     Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells

     Lamble AJ, Myers RM, Taraseviciute A, et al. · Blood Advances 2023
     used by Experiment: go back to the diagnostic sample and look for the myeloid clone before it existed, Hypothesis: the myeloid clone that appears after CD19-directed therapy was already there at diagnosis, and its abundance is a pre-treatment biomarker, Lineage switch as antigen escape from CD19-directed therapy in KMT2A-rearranged leukemia
565. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36650138
     Low input capture Hi-C (liCHi-C) identifies promoter-enhancer interactions at high-resolution

     Tomas-Daza L, Rovirosa L, Lopez-Marti P, et al. · Nature communications 2023
     used by Experiment: measure KMT2A-AFF1 spatial proximity in the human fetal progenitor, in the cell and at the time the translocation actually happens
566. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     Considerations for the Design and Conduct of Externally Controlled Trials for Drug and Biological Products: Guidance for Industry

     US Food and Drug Administration, Center for Drug Evaluation and Research · FDA guidance documents 2023
     used by External and historical controls: the design infant leukemia actually uses
567. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36280659
     Dual inhibition of EZH1/2 induces cell cycle arrest of B cell acute lymphoblastic leukemia cells through upregulation of CDKN1C and TP53INP1.

     Ito J, Yamagata K, Shinohara H, Shima Y, Katsumoto T, Aikawa Y, et al. · Int J Hematol 2023
     used by EZH1 - the paralogue that makes the approved EZH2 drug the wrong drug for this disease, EZH2 - the Polycomb enzyme that collaborates with the fusion instead of opposing it, and that no single-agent inhibitor can switch off, H3K27me3 - the repressive mark this graph argued about for seventy-seven cycles without ever writing an entry for it, Point the EED inhibitor at the index fusion - a clinical-stage drug, a subunit with no paralogue, and zero leukaemia experiments, PRC2 - the complex, not the subunit, is the unit every experiment in this disease actually resolves, Tazemetostat - an approved EZH2 inhibitor, and the drug this disease's own biology predicts will not work, Valemetostat - an approved dual EZH1/EZH2 inhibitor that has already worked in an MLL-AF4 xenograft, in a disease nobody has enrolled it in
568. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37516964
     Phase-separated nuclear bodies of nucleoporin fusions promote condensation of MLL1/CRM1 and rearrangement of 3D genome structure

     Oka M, et al. · Cell Reports 42(8):112884 2023
     used by Five KMT2A-free NUP98 fusions bind MLL1 and the NSL complex — and one unbiased mass-spectrometry study failed to reproduce it, Hypothesis: SET::NUP214 activates HOXA partly through recruited wild-type MLL1, which would make a KMT2A-unrearranged leukaemia menin-inhibitor-sensitive, NUP214 / CAN - the cytoplasmic-face nucleoporin that CRM1 docks against, and the 3' partner of four leukaemia fusions, SET::NUP214 (TAF-Ibeta-NUP214, SET-CAN), cryptic del(9)(q34.11q34.13) - a HOXA-driving fusion of a histone chaperone to a nucleoporin, with no KMT2A and no menin-binding motif, SET::NUP214 is KMT2A-free in its sequence but not in its mechanism: it binds and condenses wild-type MLL1, which reopens the menin question this beat was sent to close
569. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 34970734
     Comparison of minimal residual disease measurement by multicolour flow cytometry and PCR for fusion gene transcripts in infants with acute lymphoblastic leukaemia with KMT2A gene rearrangements.

     Popov A, Tsaur G, Verzhbitskaya T, et al. · Br J Haematol 2023
     used by Flow-cytometric MRD: the fastest readout, and the one a lineage switch walks straight out of, MRD by fusion transcript: fast, standardised, partner-limited - and structurally blind to KMT2A*, The MRD target a centre can run decides which infants are intensified, and the two targets disagree in the direction that matters, What MRD-negative actually means: a quantitative range, a laboratory judgement, and three incompatible definitions, Which MRD timepoint drives which decision in infant ALL, and how good the evidence for each is
570. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 36715125
     Genetic characteristics and treatment outcome in infants with KMT2A germline B-cell precursor acute lymphoblastic leukemia: Results of MLL-Baby protocol.

     Popov A, Tsaur G, Permikin Z, et al. · Pediatr Blood Cancer 2023
     used by Flow-cytometric MRD: the fastest readout, and the one a lineage switch walks straight out of
571. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 38016946
     Systematic characterization of the HOXA9 downstream targets in MLL-r leukemia by noncoding CRISPR screens.

     Wright S, Zhao X, Rosikiewicz W, et al. · Nat Commun 2023
     used by FLT3 / CD135 — the strongest non-tether co-dependency, and a target the field may have written off on a badly executed trial, The noncoding dependency screen five hypotheses in this graph are waiting on - and the KMT2A-rearranged screen that already exists and bounds it
572. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 36214866
     Targeting FLT3-specific chimeric antigen receptor T cells for acute lymphoblastic leukemia with KMT2A rearrangement

     Suematsu M, Yagyu S, Nagao N, Kubota S, Shimizu Y, Tanaka M, Nakazawa Y, Imamura T · Cancer Immunology, Immunotherapy 72(4):957-968 2023
     used by FLT3 in KMT2A-r leukemia — near-universal overexpression, but activating mutation in only ~3% of infants
573. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36402263
     Loss of Wdr5 attenuates MLL-rearranged leukemogenesis by suppressing Myc targets.

     Liu L, Guo X, Wang Y, et al. · Biochim Biophys Acta Mol Basis Dis 2023
     used by Four ways a WDR5 result can be true and have nothing to do with KMT2A, WDR5: an established wild-type KMT2A contact, and no fusion contact ever measured, WRAD reaches KMT2A fusions only as a passenger on a recruited wild-type complex
574. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37027891
     Mechanism of Resistance to the WDR5 Inhibitor in MLL-Rearranged Leukemia.

     Liu L, Shen L, Ding Z, et al. · ACS Chem Biol 2023
     used by Four ways a WDR5 result can be true and have nothing to do with KMT2A
575. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37423893
     Dose-dependent expression of GFI1 alters metabolism in the haematopoietic progenitors and MLL::AF9-induced leukaemic cells

     Patnana PK, Liu L, Frank D, Nimmagadda SC, Behrens M, Ahmed H, Xie X, Liebmann M, Wei L, Gerdemann A, Thivakaran A, Humpf HU, Klotz L, Dugas M, Varghese J, Trajkovic-Arsic M, Siveke JT, Hanenberg H, Opalka B, Duhrsen U, Reinhardt HC, Guenther U, von Bubnoff N, Khandanpour C · British Journal of Haematology 202:1033-1048 2023
     used by GFI1 — the repressor that LSD1 inhibitors actually work through, and the scan hit whose literature points the opposite way
576. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 36150143
     An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma.

     Izutsu K, Makita S, Nosaka K, Yoshimitsu M, Utsunomiya A, Kusumoto S, et al. · Blood 2023
     used by Giving a translocation-promoting epigenetic drug in a translocation-defined B-lineage leukaemia, to infants, Valemetostat - an approved dual EZH1/EZH2 inhibitor that has already worked in an MLL-AF4 xenograft, in a disease nobody has enrolled it in
577. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37891368
     SET-PP2A complex as a new therapeutic target in KMT2A (MLL) rearranged AML.

     Di Mambro A, et al. · Oncogene 2023
     used by GSK3 is required by KMT2A-rearranged leukaemia and nobody has shown it touches KMT2A, The phosphatase side: SET binds both wild-type KMT2A and the fusion, and inhibiting it changes four kinases at once
578. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 36882285
     The TUDOR domain of SMN is an H3K79(me1) histone mark reader.

     Binda O, Kimenyi Ishimwe AB, Galloy M, et al. · Life Sci Alliance 2023
     used by H3K79me1 - the first methyl group, the one H2B ubiquitination is not needed for, and the state HOX loci fall back to as blood cells mature
579. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36672260
     Characterization of Hepatoma-Derived Growth Factor-Related Protein 2 Interactions with Heterochromatin.

     Wistner SC, et al. · Cells 2023;12 2023
     used by HDGFL2 / HRP-2 - the second IBD protein, which binds KMT2A at the same site with the same affinity and does NOT need menin to do it
580. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 36988711
     HERV-K (HML-2) insertion polymorphisms in the 8q24.13 region and their potential etiological associations with acute myeloid leukemia

     Camargo-Forero N, Orozco-Arias S, Perez Agudelo JM, Guyot R · Archives of Virology 2023
     used by Hypothesis: t(4;11) infant ALL is a hypermethylated genome whose transposable elements can be reawakened, and that reawakening is an untested immunotherapeutic lever
581. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37752126
     Late effects in survivors of infant acute lymphoblastic leukaemia-a study of the Australian and New Zealand Children's Haematology/Oncology Group.

     Mironova D, Saraswati CM, Downie P, Lai CY, Cook E, Carruthers V, et al. · Blood Cancer J 2023
     used by Hypothesis: the spread in infant presenting-feature frequencies is mostly measurement, not biology, Kotecha group, Perth: the infant KMT2A-rearranged laboratory this graph had cited once, Nine survivors in ten carry a long-term complication, and it is worse the younger they were, The ANZCHOG infant cohort: 119 babies, with the presenting features actually tabulated, Two cohorts, a hundred infants each, and opposite answers on which sex does worse
582. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37516825
     METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer

     García-Vílchez R, Añazco-Guenkova AM, Dietmann S, López J, Morón-Calvente V, D'Ambrosi S, Nombela P, Zamacola K, Mendizabal I, García-Longarte S, Zabala-Letona A, Astobiza I, Fernández S, Paniagua A, Miguel-López B, Marchand V, Alonso-López D, Merkel A, García-Tuñón I, Ugalde-Olano A, Loizaga-Iriarte A, Lacasa-Viscasillas I, Unda M, Azkargorta M, Elortza F, Bárcena L, Gonzalez-Lopez M, Aransay AM, Di Domenico T, Sánchez-Martín MA, De Las Rivas J, Guil S, Motorin Y, Helm M, Pandolfi PP, Carracedo A, Blanco S · Molecular Cancer 2023
     used by Hypothesis: transfer-RNA and ribosome biology is a genuinely empty cell in KMT2A-rearranged leukemia, and translational capacity may be the unmeasured dependency
583. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37872214
     Low doses of IFN-gamma maintain self-renewal of leukemia stem cells in acute myeloid leukemia.

     Xie X, Zhang W, Zhou X, Xu B, Wang H, Qiu Y, et al. · Oncogene 2023
     used by IFNGR1 - the receptor the whole antigen-presentation mechanism runs through, and the one where low-dose interferon-gamma makes MLL-fusion leukaemia worse
584. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37143651
     Insights into IGH clonal evolution in BCP-ALL: frequency, mechanisms, associations, and diagnostic implications.

     Darzentas F, Szczepanowski M, Kotrová M, et al. · Front Immunol 2023
     used by Ig-based MRD fails specifically in the KMT2A-rearranged patients whose IGH repertoire is proximally biased and still recombining, MRD by Ig/TCR rearrangement: the standard in ALL, and the assay infant KMT2A-rearranged disease strains hardest, Proximally biased V(D)J and IGHV6-1 in KMT2A::AFF1: the Ig MRD target is a moving target, and the clinic had already moved, Retrospective paired-target MRD on stored Interfant marrows, stratified by IGHV usage, Sequencing-based MRD: better than flow in paediatric B-ALL, and applied to infant KMT2A-rearranged disease exactly once
585. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37670323
     RNA binding protein IGF2BP1 synergizes with ETV6-RUNX1 to drive oncogenic signaling in B-cell Acute Lymphoblastic Leukemia

     Sharma G, et al. · J Exp Clin Cancer Res 2023
     used by IGF2BP1 — the IMP paralogue that belongs to a DIFFERENT fusion, and the cleanest control the family offers
586. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37595275
     Genetic alterations and MRD refine risk assessment for KMT2A-rearranged B-cell precursor ALL in adults: a GRAALL study.

     Kim R, Bergugnat H, Pastoret C, et al. · Blood 2023
     used by IKZF1 - the defining co-lesion of every other high-risk B-ALL, and this disease does not use it until after treatment, The quiet genome, audited - the famous 1.3 mutations is a count of point mutations in the dominant clone, and all three of those words do work, TP53 - named in 84 entries of this graph, absent from the index genome study of the disease, and four different things depending on when you look
587. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37639801
     Generation of a human induced pluripotent stem cell line harboring the infant leukemia-associated fusion gene, KMT2A-AFF1 (IMSUTi002-A-2)

     Takahashi M · Stem Cell Research 2023
     used by IMSUTi002-A-2 (CVCL_C9HE) — a doxycycline-inducible KMT2A::AFF1 iPSC line, and the isogenic design nobody in this graph has used
588. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.preprint
     CRISPR-ChIP delineates a Menin-dependent oncogenic DOT1L complex in MLL-leukaemia

     Gilan O, Bell C, Talarmain L, Neville D, Knezevic K, Ferguson D, Boudes M, Chan Y-c, Davidovich C, Lam E, Dawson MA · bioRxiv 2023
     used by In KMT2A::AFF1 there is no oncogenic DOT1L unit: all H3K79 methylation is the endogenous MLLT10-directed activity, working on genes the fusion has opened
589. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 37520776
     The MLL-Menin Interaction is a Therapeutic Vulnerability in NUP98-rearranged AML

     Rasouli M, et al. · HemaSphere 7(8):e935 2023
     used by In NUP98-rearranged leukaemia, who responds to a menin inhibitor is decided by the co-mutations, not by the fusion, NUP98::NSD1 without FLT3-ITD loses its prognostic significance — the confound that undermines the fusion's own reputation, NUP98::NSD1, t(5;11)(q35;p15.5), SAVE (NCT05360160): the first prospective menin-inhibitor trial to report a NUP98-rearranged subgroup outcome, The first published complete remission of NUP98-rearranged AML on a menin inhibitor (icovamenib/BMF-219, n=1), Why a nucleoporin fusion needs menin-MLL1: the second menin-dependent fusion family, and what it borrows rather than carries
590. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36815378
     Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia

     Bertrums EJM, et al. · Haematologica 108(8):2044-2058 2023
     used by In NUP98-rearranged leukaemia, who responds to a menin inhibitor is decided by the co-mutations, not by the fusion, NUP98 rearrangements are 7.2% of paediatric AML and 1.6% of adult, with 35% five-year overall survival — and the partner changes everything, NUP98::NSD1 without FLT3-ITD loses its prognostic significance — the confound that undermines the fusion's own reputation, NUP98::TOP1, t(11;20)(p15;q11~q12) — the most precisely mapped NUP98 breakpoint, and the reciprocal that was wrong twice
591. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 36706271
     Successful Retransplantation With Killer Cell Immunoglobulin-like Receptor Ligand-mismatched Cord Blood in Infant Acute Lymphoblastic Leukemia That Relapsed After Transplantation.

     Mizuki K, Honda Y, Asai H, Higuchi N, Morita H, Yabe H, Kusuhara K · J Pediatr Hematol Oncol 2023
     used by In this fusion family, MHC class I is not silenced - it is elevated and load-bearing, holding NK cells off the leukaemia stem cell, The NK cell - the effector arm of haploidentical transplant, the one this disease is documented to evade, and the cell CLEC12A was named on
592. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 36833225
     The Role of IRX Homeobox Genes in Hematopoietic Progenitors and Leukemia

     Nagel S · Genes (Basel) 14:297 2023
     used by IRX1 fusion occupancy is confined to KMT2A::AFF1: 0 of 18 samples across five other partners, IRX2 transcript is NOT AFF1-confined: re-deriving GSE68720 finds 1 of 16 KMT2A::MLLT1 infants positive, and that case is IRX2-positive with IRX1 off
593. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB 7RZD: CRYSTAL STRUCTURE OF HLA-B*07:02 IN COMPLEX WITH MLL(747-755) PEPTIDE

     Patskovsky Y, Natarajan A, Patskovska L, et al. · RCSB Protein Data Bank 2023
     used by KMT2A 747-755 on HLA-B*07:02: a phosphoneoantigen from the half of KMT2A every fusion keeps, with seven crystal structures and a cognate TCR
594. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
     PDB 7RZJ: CRYSTAL STRUCTURE OF HLA-B*07:02 IN COMPLEX WITH MLL(747-755) PHOSPHOPEPTIDE

     Patskovsky Y, Natarajan A, Patskovska L, et al. · RCSB Protein Data Bank 2023
     used by KMT2A 747-755 on HLA-B*07:02: a phosphoneoantigen from the half of KMT2A every fusion keeps, with seven crystal structures and a cognate TCR
595. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36598580
     Clustered PHD domains in KMT2/MLL proteins are attracted by H3K4me3 and H3 acetylation-rich active promoters and enhancers

     Stroynowska-Czerwinska AM, Klimczak M, Pastor M, et al. · Cellular and Molecular Life Sciences 2023
     used by KMT2A minor breakpoint cluster region (BCR2): intron 20 - exon 24, Nuclear import of every KMT2A fusion is a property of retained KMT2A sequence, and the determinant was mapped in 1997 to a region containing the AT-hook motifs, The clustered PHD fingers (KMT2A aa 1416-1640) are a chromatin-targeting module and the canonical t(4;11) junction removes them by ten residues
596. strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 36931259
     A central chaperone-like role for 14-3-3 proteins in human cells.

     Segal D, et al. · Mol Cell 2023
     used by KMT2A sits in the 14-3-3 proximity neighbourhood, and the YWHAG link reproduces across two independent studies, Looking for a second handle on the retained fragment, and not finding one, One immunoprecipitation that decides whether 14-3-3 touches KMT2A at all, YWHAG / 14-3-3 gamma (P61981) - the only cross-laboratory reproduced KMT2A proximity partner in the curated record, and UniProt places it nowhere near the nucleus
597. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 37788672
     Cryo-EM structure of the KLHL22 E3 ligase bound to an oligomeric metabolic enzyme.

     Teng F, Wang Y, Liu M, Tian S, Stjepanovic G, Su MY · Structure 2023
     used by KMT2A-KLHL22 - DECLINED. The single source is a cryo-EM structure of KLHL22-CUL3 bound to glutamate dehydrogenase, and KMT2A is a HEK293F pull-down passenger with no nuclear rationale
598. established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
     A Molecular Switch between Mammalian MLL Complexes Dictates Response to Menin-MLL Inhibition (GSE186711)

     GEO submitters · NCBI Gene Expression Omnibus 2023
     used by KMT2A-rearranged or NPM1-mutant? Both, in separate arms: WT-MA9 mouse, MOLM13, OCI-AML3, and two patients on AUGMENT-101, The prescribed GEO lookup returns zero for every paper this project has ever resolved, including the one it was written from
599. moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 37517063
     Rearrangement of KMT2A Characterizes a Subset of Pediatric Parotid Mucoepidermoid Carcinomas Arising Metachronous to Acute Lymphoblastic Leukemia.

     Othman BK, Steiner P, Leivo I, Skálová A · Fetal and Pediatric Pathology 2023
     used by KMT2A::MAML2 type B2/B3 thymoma - the same fusion, a different organ, a different disease
600. weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 37803862
     [Two cases of refractory childhood acute B-lymphoblastic leukemia with positive KMT2A-USP2 treated with Belintouximab].

     Sun Y, Ni YA, Xu HJ, Wang LZ, Yang J, Jiang J, Zhong R · Zhonghua Er Ke Za Zhi (Chinese Journal of Pediatrics) 2023
     used by KMT2A::USP2, inv(11)(q23.3q23.3) - the minor-BCR fusion that keeps the PHD fingers