JAK1 - recruited and stabilised by AF10 fusions, and the kinase whose downstream STAT1 the class I effect of menin inhibition explicitly does not need

[
  "JAK1A",
  "JAK1B"
]

{
  "fusions": [
    "KMT2A::MLLT10",
    "PICALM::MLLT10"
  ],
  "nature": "direct recruitment and stabilisation of JAK1 by the fusion; no phosphosite on the fusion mapped",
  "pmid": "33690798",
  "graph_entry": "interface-jak1-mllt10-fusion-kinase-contact-no-site",
  "title": "A JAK/STAT-mediated inflammatory signaling cascade drives oncogenesis in AF10-rearranged AML.",
  "authors": "Chen BR, Deshpande A, Barbosa K, et al.",
  "venue": "Blood",
  "year": 2021,
  "title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
}

{
  "stat1_required": false,
  "ifih1_mda5_required": false,
  "rela_required": false,
  "pmid": "36635503",
  "title": "Targeting Menin disrupts the KMT2A/B and polycomb balance to paradoxically activate bivalent genes.",
  "authors": "Sparbier CE, Gillespie A, Gomez J, et al.",
  "venue": "Nat Cell Biol",
  "year": 2023,
  "title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
}

{
  "chronos_mean_kmt2a_rearranged": 0.0171,
  "chronos_mean_other_leukaemia": -0.1955,
  "difference": 0.2126,
  "pan_essentiality_all_lines": -0.0685,
  "selectivity_rank": 17614,
  "rank_denominator": 17728,
  "provenance": "Joined 2026-09-21 from analyses/depmap-kmt2a-selective-scan-full (generated 2026-09-19T10:12:06Z), the project's own genome-wide scan over 11 KMT2A-rearranged and 43 other leukaemia DepMap lines. NOT re-fetched and NOT independent of that scan: every caveat it carries applies here, including that the KMT2A-rearranged arm is a small number of lines drawn from nine individuals, that the rank denominator is 17,728 genes, and that a difference is not a dependency. Added because only 26 of 308 gene entries carried this number, which made any KMT2A-selectivity question answerable for 8% of the corpus.",
  "how_to_read": "A negative difference means MORE required in KMT2A-rearranged lines than in other leukaemia lines. A rank near 17,728 is ANTI-selective. Neither is evidence of a fusion-driven dependency on its own: check pan_essentiality_all_lines before calling anything selective, and note that a paralogue-redundant gene can score near zero for reasons that have nothing to do with this disease - see ana-the-paralogue-redundancy-excuse-is-not-tested-and-my-proxy-decided-the-answer."
}

{
  "CONSTITUTIVE": "CYTOPLASMIC AND NUCLEAR, and UNIPROT RECORDS NEITHER. P23458 (fetched live 2026-09-21) carries exactly ONE SUBCELLULAR LOCATION value - 'Endomembrane system', topology 'Peripheral membrane protein' - and BOTH have an EMPTY EVIDENCE LIST: no ECO:0000269, no ECO:0000250, no PROSITE or HAMAP rule. The accompanying note is itself hedged: 'Wholly intracellular, possibly membrane associated'. There is NO nucleus value on the record at all [E_q93_jak1_loc1].",
  "THE_BRIEF_ASKED_WHETHER_THE_NUCLEAR_POOL_IS_REAL_AND_THE_ANSWER_INVERTS_THE_QUESTION": "It is real, it is mechanistically mapped, and the database error runs in the OPPOSITE direction from the one the brief anticipated - UniProt UNDERSTATES this protein's compartment to the point of having no nucleus for it. JAK1 has a CLASSICAL NUCLEAR LOCALIZATION SIGNAL toward the N-terminal region, recognised by MULTIPLE IMPORTIN-ALPHA ISOFORMS; nuclear import is INDEPENDENT OF ITS KINASE ACTIVITY and is required for optimal expansion of activated-B-cell-like diffuse large B-cell lymphoma cells [E_q93_jak1_loc2]. Constitutive nucleocytoplasmic distribution of JAK1 and JAK2 was reported as far back as 1996, by immunocytochemistry and by western blot of purified nuclear extracts, and for JAK1 the nuclear content did not change on ligand stimulation [E_q93_jak1_loc3].",
  "THE_ANNOTATION_CLASS_IS_THE_SAME_AS_MAP3K14_AND_THAT_IS_NOW_TWICE": "Tranche 3 recorded that MAP3K14's single 'Cytoplasm' value has an empty evidence list and called it the weakest annotation class that tranche encountered. JAK1 is the second instance and it is worse, because MAP3K14's unsourced call is at least consistent with its mechanism whereas JAK1's is a compartment ('Endomembrane system') that no paper cited here measures, on a protein whose nuclear pool has a mapped import pathway. TWO OF THIS GRAPH'S SIGNALLING KINASES HAVE UNIPROT COMPARTMENTS WITH NO EVIDENCE BEHIND THEM.",
  "how_shown": "classical-NLS mapping with importin-alpha isoform binding and a kinase-dead separation-of-function in ABC DLBCL lines (2017); immunocytochemistry plus western blot of purified nuclear extracts in CHO cells expressing the rat GH receptor, with immunogold electron microscopy for JAK2 (1996)",
  "systems": "human ABC DLBCL cell lines - B-LINEAGE, which is unusually apposite for this disease - and CHO cells plus rat hepatocytes for the older work. No leukaemic cell and no KMT2A-rearranged cell",
  "node": "localization-chromatin-bound-versus-soluble-fraction-kmt2a"
}

{
  "measured_in": "ABC DLBCL cell lines for the nuclear-import requirement [E_q93_jak1_loc2]; CHO cells transfected with rat GH receptor cDNA and rat liver hepatocytes for the 1996 constitutive-nuclear work [E_q93_jak1_loc3].",
  "the_B_LINEAGE_point": "The one cell type in which JAK1's nuclear pool has been shown to MATTER is a B-cell malignancy: nuclear import of JAK1 is required for the optimal expansion of ABC DLBCL cells in vitro, and the authors propose targeting JAK1 nuclear localisation as a strategy there. This graph's disease is B-lineage, and 39% of its load-bearing evidence carries no experimental-system marker at all, so a B-lineage localisation requirement on a gene already in the graph is worth naming precisely: ABC DLBCL is a mature-B lymphoma, NOT an infant pro-B leukaemia, and nothing transfers without being tested.",
  "expression": "UniProt P23458's tissue comment is about colon tumour versus normal colon and carries no haematopoietic information at all. JAKs are described as especially important in haematopoiesis, inflammation and immunity in the review cited here [E_q93_jak1_loc5], which is background rather than a measurement.",
  "in_this_disease": "JAK1 is PHYSICALLY BOUND to a KMT2A fusion - this entry's existing E1 records AF10 fusion proteins activating a JAK/STAT inflammatory cascade through direct recruitment of JAK1, with higher JAK1 protein and unchanged mRNA - and there is NO localisation measurement in that system or any other KMT2A-rearranged cell. So this gene has a demonstrated fusion CONTACT and a demonstrated NUCLEAR IMPORT PATHWAY and nobody has put the two in the same experiment."
}

{
  "state": "HIGH-PROLIFERATION / AUTOCRINE-CYTOKINE, as the condition under which the nuclear pool is reported. The review framing is explicit: JAK1 and JAK2 are present in the nucleus of certain cells OFTEN UNDER CONDITIONS ASSOCIATED WITH HIGH RATES OF CELL GROWTH [E_q93_jak1_loc5], and in ABC DLBCL the relevant upstream is autocrine IL6 and IL10 [E_q93_jak1_loc2].",
  "and_one_measurement_says_the_pool_is_NOT_stimulus_dependent": "The 1996 study found NO CHANGE in the nuclear content of JAK1 or JAK2 after 5 to 60 minutes of growth-hormone stimulation, although stimulation did put tyrosine-phosphorylated JAK2 into the nucleus [E_q93_jak1_loc3]. So the resting nuclear pool appears constitutive while the ACTIVATED nuclear pool is inducible - abundance and phosphorylation state are two different variables and the older literature separates them.",
  "bounded": "No JAK1 localisation or cell-state compartment measurement exists in any leukaemic cell, and nothing under a menin inhibitor. This entry's existing menin_route_independence block records that the class I effect of menin inhibition does not require STAT1, which is a pathway result and not a compartment one."
}

{
  "date": "2026-09-21",
  "tool": "NCBI E-utilities esearch, db=pubmed",
  "run_by": "Q93",
  "queries": [
    {
      "query": "(\"JAK1\"[tiab] OR \"Janus kinase 1\"[tiab])",
      "querytranslation": "\"JAK1\"[Title/Abstract] OR \"Janus kinase 1\"[Title/Abstract]",
      "count": 6382,
      "role": "operand control"
    },
    {
      "query": "(gene clause) AND (twelve-term subnuclear clause)",
      "count": 4,
      "title_check": "0 of 4 on topic. PMID 38924373 (SNORA28 in colorectal cancer), 34502232 (radiation-induced osteocyte senescence), 30767270 (SNHG20 in oesophageal cancer), 27860076 (HPV16 genome loss in PML-protein-deficient keratinocytes). Note the mechanism of contamination: 'nucleolar' inside 'small nucleolar RNA' pulls in the entire snoRNA and SNHG literature.",
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    },
    {
      "query": "JAK1[tiab] AND \"nuclear\"[ti]",
      "querytranslation": "\"JAK1\"[Title/Abstract] AND \"nuclear\"[Title]",
      "count": 19,
      "title_check": "3 on topic and they are the three cited here: PMID 28031410 (nuclear import of JAK1 via a classical NLS), 8756581 (constitutive nuclear localization of JAK1 and JAK2), 21892841 (review: JAKs go nuclear). The other 16 are NUCLEAR FACTOR-kappaB, nuclear factor erythroid-2-like 2, hepatocyte nuclear factor, nuclear-enriched abundant transcript 1 and similar - 'nuclear' as the first word of another gene's name."
    },
    {
      "query": "(gene clause) AND (nine-term KMT2A/MLL fusion clause)",
      "count": 8,
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    },
    {
      "query": "(gene clause) AND (localisation clause) AND (fusion clause)",
      "count": 0,
      "role": "the load-bearing zero",
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    }
  ],
  "A_NEW_CONTAMINATED_TOKEN_WORTH_THE_REGISTRY": "'nucleolar'[tiab] is contaminated for any RNA-binding or RNA-adjacent gene, because SMALL NUCLEOLAR RNA and its host-gene family (SNHG1, SNHG4, SNHG12, SNHG20, SNORD9, SNORD78, SNORA28) match it. On JAK1 it produced 3 of 4 off-topic hits and on IGF2BP2 in this same tranche it produced 7 of 7. This is the same family as the logged 'speckle*' contamination, and it bites hardest on exactly the genes a localisation beat most wants to place in a nucleolus.",
  "reading": "Titles and abstracts only; supporting figures not searched (brief rule 80).",
  "absence_class": "never-measured"
}