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
also called Q115 gained-occupancy re-bound · GSE260742 desk job
Nobody has checked whether the leukaemia fusion protein moves to new places on the DNA when the drug knocks it off its usual ones, and searching whole papers rather than summaries does not turn up anyone who has. What has changed is that somebody has now deposited exactly the right experiment publicly, without asking that question of it.
The same thing, for a scientist
`absence-no-study-has-tested-for-gained-fusion-occupancy-under-menin-inhibition` is bounded by a 21-name `[tiab]` query. Re-run against Europe PMC full text with a 20-name menin-inhibitor list and a nine-term gain vocabulary (`gained peaks`, `gained sites`, `de novo peaks`, `new binding sites`, `newly gained`, `gained occupancy`, `redistributed`, `relocalized`, `relocalised`): **28 records, and 16 when intersected with a ChIP method term** [E1]. Every title was read. **None tests for gained occupancy by a KMT2A fusion under a menin inhibitor.** The nearest neighbour is PMID 39806204, *Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters* - off-scope on both axes named in its own title: the tissue is urothelium and the perturbation is Kmt2c/Kmt2d loss, not a menin inhibitor, and the protein is wild-type KMT2A-menin, not a fusion [E2]. **The upgrade is the deposit.** PMID 41634341 performed FLAG-MLLAF9 ChIP-seq in murine MLLAF9 cells under VTP50469 (500 nM, 48 h) against DMSO, with spike-in normalisation (ChIP-Rx) for the H2AK119ub arm, and deposited it: **GSE260742, 158 samples, BioProject PRJNA1083204**, verified live [E3]. Its own analysis ranks genes *from highest to lowest by MLLAF9 occupancy in DMSO* and asks what is lost; the word `gained` occurs twice in its 142,856-character full text and refers to H2AK119ub both times [E4]. **The gain-calling analysis is compute on public data.**
What the deposit can and cannot answer
Can. Call peaks on FLAG-MLLAF9 in DMSO and in VTP50469 separately rather than ranking the DMSO set, and count sites present in treated and absent in control. That is the exact question the entry poses, it needs no wet work, and the series includes the matched inputs.
Cannot. The fusion is MLLAF9 in a murine line, not the index human KMT2A::AFF1, and it is FLAG-tagged - so a gain could be a property of the tag, of the mouse, or of that partner. The entry's claim is about KMT2A fusions generally and the strongest available test of it is now one fusion in one species. A negative would be informative and a positive would need the human line before it meant anything.
And the analysis has a known trap. A drug that removes most of a protein from chromatin changes the library composition, so read-depth normalisation alone will manufacture apparent gains at every site that loses least. The deposit's ChIP-Rx spike-in is the reason this is tractable at all, and any gain-call that does not use it is measuring normalisation.
The bounded rejections - what was read and put down
Of the 28 full-text records, the ones a reader would reasonably expect to be cited and which are not:
- PMID 41192422, Disparate leukemia mutations converge on nuclear phase-separated condensates, Cell 2025. On-topic vocabulary, not opened by this beat. If it images or ChIPs a fusion under a menin inhibitor and reports relocation, it overturns the entry. This is the single most likely refutation and it is unread.
- PMID 39850646, Mastering fate: Redistributing a pioneer protein to rewrite leukemia's script, HemaSphere 2025 - a commentary, so not a primary observation, but it names redistribution in a leukaemia context.
- PMID 37055414, Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor, Blood Cancer J 2023 - menin inhibitor plus chromatin, read at title level as a combination-efficacy study, not an occupancy-gain study.
- Four of the 28 and four of the 16 are congress abstract books.
| script | none - Europe PMC BODY: queries, one full-text read, one GEO SOFT read; 2026-09-22 |
|---|---|
| status | run |
| verdict | SURVIVES at full text, and the absence CLASS is upgraded: an accession now exists |
| entry re bounded | absence-no-study-has-tested-for-gained-fusion-occupancy-under-menin-inhibition |
| instrument before | abstract-level literature search over a 21-name drug list |
| instrument after | full-text search over 12,362,145 Europe PMC full texts, plus a GEO series record read |
| accession that closes it | GSE260742 |
| the analysis that would close it | Call peaks independently on FLAG-MLLAF9 in DMSO and in VTP50469 with the matched inputs and spike-in normalisation, then count treated-present/control-absent sites. The paper ranked the DMSO set instead, which cannot show a gain by construction. |
| absence class | measured-not-analysed |
| absence class basis | CHANGED BY THIS RE-BOUND. The entry under test carries measured-not-analysed on the strength of eight occupancy datasets identified from abstracts. GSE260742 is a better instance and a specific one: FLAG-MLLAF9 ChIP-seq under VTP50469 with matched DMSO and spike-in normalisation, deposited 2026, 158 samples, live at the SOFT endpoint on 2026-09-22. The gain analysis has never been run on it. |
| absence class assigned | 2026-09-22 (Q115) |
queries — the numbers behind the chart
[
{
"q": "menin-inhibitor list (20 names) AND gain vocabulary (9 terms)",
"hits": 28,
"on_topic": 0,
"proceedings": 4
},
{
"q": "the same AND (ChIP-seq OR ChIP-Rx OR CUT&RUN)",
"hits": 16,
"on_topic": 0,
"proceedings": 4
},
{
"q": "gain vocabulary alone",
"hits": 41569,
"role": "operand control"
},
{
"q": "menin-inhibitor list alone",
"hits": 1218,
"role": "operand control"
}
]gain vocabulary
[ "gained peaks", "gained sites", "de novo peaks", "new binding sites", "newly gained", "gained occupancy", "redistributed", "relocalized", "relocalised" ]
drug name list
[ "revumenib", "ziftomenib", "bleximenib", "enzomenib", "VTP-50469", "SNDX-5613", "KO-539", "MI-503", "MI-3454", "MI-2-2", "MI-463", "MI-538", "JNJ-75276617", "DSP-5336", "DS-1594", "BMF-219", "icovamenib", "menin inhibitor", "menin inhibitors", "menin inhibition" ]
accession details
{
"samples": 158,
"bioproject": "PRJNA1083204",
"contents": "FLAG-MLLAF9 (murine) and MOLM13 and K562 ChIP-seq +/- DOT1L or menin inhibitor; HuDEP-2 and mESC +/- DOT1L inhibitor",
"treatment": "VTP50469 500 nM 48 h, SGC0946 5 uM 48 h, versus DMSO",
"spike_in": "ChIP-Rx used for the H2AK119ub arm",
"companion_rnaseq": "GSE260456",
"third_party_series_used_by_the_paper": "GSE181829 (MLL1 ChIP-seq in K562 under a menin inhibitor)"
}not read — the numbers behind the chart
[
{
"pmid": "41192422",
"title": "Disparate leukemia mutations converge on nuclear phase-separated condensates.",
"venue": "Cell",
"year": 2025,
"why_it_matters": "the most likely refutation in the hit list; condensate relocation under a menin inhibitor would overturn the entry"
},
{
"pmid": "39850646",
"title": "Mastering fate: Redistributing a pioneer protein to rewrite leukemia's script.",
"venue": "HemaSphere",
"year": 2025,
"why_it_matters": "a commentary naming redistribution in leukaemia"
},
{
"pmid": "39806204",
"title": "Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.",
"venue": "Nature Genetics",
"year": 2025,
"why_it_matters": "the only paper found that reports KMT2A-menin redistribution at all"
}
]- If a menin inhibitor relocates rather than removes the fusion, the drug's clinical benefit and its long-term risk decouple: blasts differentiate because the old sites are vacated, while a new occupancy pattern is laid down that nobody is monitoring and that no response criterion would detect.
- A gain analysis on spike-in-normalised data can produce a confident artefact in the opposite direction too. If the spike-in fraction shifts with treatment-induced cell death, apparent gains and apparent losses both scale, and the result would look like a mechanism.
- Which of the 158 GSE260742 samples are FLAG pulldowns under VTP50469, and how many replicates with matched input? The per-GSM records decide whether the gain call is powered and nobody has read them.
- Does PMID 41192422 report fusion relocation under a menin inhibitor? It is the one unread record in the hit list that could overturn this absence outright.
- Would the same gain call on GSE181829 - MLL1 ChIP-seq in K562 under a menin inhibitor, which the depositing paper reused - answer the question for WILD-TYPE KMT2A, giving the comparator the fusion analysis needs?
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
A 20-name menin-inhibitor list crossed with a nine-term gain vocabulary over Europe PMC full text returns 28 records, 16 when further intersected with ChIP-seq / ChIP-Rx / CUT&RUN, and no title among them is a test of gained fusion occupancy under a menin inhibitor.
Europe PMC RESTful search, BODY: full-text field, menin-inhibitor name list x gain vocabulary, run 2026-09-22 · Europe PMC 2026What this evidence cannot show
Operand control through the same template: the gain vocabulary alone returns 41,569 and the drug list alone 1,218, so the conjunction is doing the work and neither clause is dead. Screening was at TITLE level for all 28; three were judged on title alone and are named as unread in data.not_read. A gain reported only in a supplementary figure with no gain word in the body would be invisible even here.
Evidence that argues against this (1)
- The gain vocabulary is a name list and rule 70 applies to it. A paper writing 'novel sites', 'ectopic binding', 'off-target recruitment' or 'spreading' would not match. The list was not extended to those and the absence is bounded by the nine terms used, which are recorded. Europe PMC 2026
- E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
The nearest full-text neighbour reports redistribution of KMT2A-menin to bivalent promoters, but in urothelium and driven by Kmt2c or Kmt2d loss rather than by a menin inhibitor, and for wild-type KMT2A rather than a fusion.
Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters. · Nature Genetics 2025What this evidence cannot show
TITLE-CHECKED ONLY, not opened. The title was taken from the full Europe PMC record rather than from a truncated listing. Every disqualifying feature quoted here - urothelium, Kmt2c/Kmt2d loss, KMT2A-menin - is stated in the title itself, so the exclusion does not depend on the body; but a menin-inhibitor arm inside the paper would change the verdict and cannot be excluded without reading it.
Evidence that argues against this (1)
- This paper is direct evidence that the KMT2A-menin module CAN redistribute rather than simply be lost, in a real tissue, under a genetic perturbation. That is the mechanistic premise the absence entry says has never been tested pharmacologically - so it strengthens the entry's motivation while leaving its claim intact, and a beat that opened it might find the drug arm. Nature Genetics 2025
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
GSE260742 is live and holds 158 ChIP-seq samples: ChIP sequencing of murine FLAG-MLLAF9 and MOLM13 AML lines and K562 with and without DOT1L or Menin inhibitor treatment, plus HuDEP-2 and mouse ES cells with and without DOT1L inhibitor; BioProject PRJNA1083204.
NCBI GEO series GSE260742 - DOT1L provides transcriptional memory through PRC1.1 antagonism [ChIP-Seq] · NCBI Gene Expression Omnibus 2026What this evidence cannot show
Read 2026-09-22 from the SOFT text view, which is authoritative and not behind bot detection; the 158 count is a direct count of !Series_sample_id lines (111 in the GSM8123342-8123452 block plus 47 in the GSM8549820-8549866 block). The series description names the antibodies at the series level only - which of the 158 samples are FLAG pulldowns under VTP50469 must be read per-GSM and was NOT done here.
Evidence that argues against this (1)
- A series-level description is not a sample manifest. Until the per-GSM records are read, the number of FLAG-MLLAF9 samples under menin inhibitor with matched input could be as few as two, which would make peak calling underpowered for gains and would change the recommendation from 'desk job' to 'desk job that may not be conclusive'. NCBI Gene Expression Omnibus 2026
- E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The depositing paper analyses its FLAG-MLLAF9 ChIP-seq by ranking genes from highest to lowest MLLAF9 occupancy in DMSO and asking what is lost; the string 'gained' appears twice in its full text and refers to H2AK119ub on both occasions.
DOT1L provides transcriptional memory through PRC1.1 antagonism. · Nature Cell Biology 2026What this evidence cannot show
Counted on the retrieved fullTextXML (PMC12904788, 142,856 characters) on 2026-09-22. A word count is a statement about the prose, not about the analysis: the authors state their conclusion that PRC1.1 deposition is 'independent of MLL-FP displacement', which implies they looked at fusion occupancy, and a supplementary figure could contain a gain analysis the text does not describe. Supplementary files were not opened.
Evidence that argues against this (1)
- The authors' own framing - that the effect is independent of MLL-FP displacement - is the strongest available argument that they did examine fusion occupancy carefully. If their extended data contain a gained-peak count, this absence is measured-not-reported rather than measured-not-analysed, and closes by opening a supplement. Nature Cell Biology 2026
SURVIVES at full text (28 records, 0 on topic) and the class upgrades: GSE260742 holds FLAG-MLLAF9 ChIP-seq under VTP50469 and the gain call was never made
names the deposit behind that mechanism entry as the instrument for a question its own paper did not ask
the unmeasured behaviour of the fusion under this drug class: relocation versus removal
the cycle-65 entry's 'spike-in normalised FLAG-MLLAF9 under VTP50469' is not supported by the deposit: 0 of 158 sample records mention a spike-in and the paper's only ChIP-Rx panel is H2AK119ub
runs the analysis that entry said was a desk job; the answer is eviction without redistribution to a recognisable programme