Oncofusion

start / graph / absence-no-cell-state-for-ash2l

Analysisstrong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.Q60-cellstate2

ASH2L is studied in leukaemia and has never been placed in a cell state there — and the KMT2A-rearranged arm needs it LESS than average

also called ASH2L bounded cell-state absence

ASH2L is part of the machine at the centre of this disease, and there are leukaemia papers about it, but none asks what condition it holds a cell in. The big cancer screen also finds that leukaemias with this fusion need ASH2L slightly less than other cancers do.

The same thing, for a scientist

Bounded query on 2026-09-20: `(ASH2L OR ASH2 OR ASH2L1)[tiab] AND <18-term cell-state clause> AND <leukaemia clause>` returns **1**, a mouse embryonic-stem-cell paper [E1]. Unscoped the gene-plus-state query returns 4 and every one is non-haematopoietic: Drosophila oocyte, melanoma, pluripotency, mouse ES cells. ASH2L does have a leukaemia literature — PMID 32021283 on ASH2L-promoted HOXC8 expression in MLL-rearranged acute leukaemia, and PMID 31870784 on ASH2L and BCL-X under glucocorticoids — but neither measures a cell state [E2]. And the requirement evidence points away: in DepMap the KMT2A-rearranged arm is **+0.157 relative to all lines**, the only positive non-floor-compressed contrast in this beat's worklist [E3].

Go deeper
Rule 80 was run and the absence held, with an instructive detail

PMID 32021283 was opened via PMC6969701, 27,316 characters. The only cell-state word anywhere in it is stemness, and that single occurrence is inside a reference title, not in the paper's own text 2. The absence held.

PMID 31870784 (Glucocorticoids uncover a critical role for ASH2L on BCL-X expression regulation in leukemia cells) could not be read: Europe PMC core returns no PMCID and efetch db=pubmed carries no <ArticleId IdType="pmc">, so routes 2-4 were structurally unavailable. It is recorded as known-but-unreadable, not as an absence, per concept-known-but-unreadable-literature.

Structure is not requirement, and this is the case that shows it

ASH2L reaches degree 23 in this graph on the strength of its structural and biochemical position in the MLL core complex — it is the subunit DPY30 stabilises, it contacts the SPRY and the nucleosome, and its residue numbering is the subject of a documented 94-residue offset trap in this brief.

None of that is evidence that KMT2A-rearranged cells need it, and the one measurement available says they need it slightly less than the average cancer line 3. The graph should not let structural centrality stand in for a dependency claim.

Facts and figures
genegene-ash2l
symbolASH2L
uniprotQ9UBL3
length AA628
statusrun
query(ASH2L[tiab] OR "ASH2"[tiab] OR "ASH2L1"[tiab]) AND <cell-state clause> AND <leukaemia clause>
count1
on topic after title check0
on topic after opening full texts0
gene clause alone control322
unscoped count4
complex form query("WRAD"[tiab] OR "COMPASS complex"[tiab] OR "MLL complex"[tiab] OR "SET1/MLL"[tiab]) AND <cell-state clause>
complex form count17
depmap contrast A0.157
result summaryASH2L has leukaemia papers but no cell-state characterisation there, and the KMT2A-rearranged arm is less dependent on it than the average line.
state clause alone control96743
date2026-09-20
toolNCBI esearch db=pubmed
absence classmeasured-not-analysed
absence class basisARCHIVE CHECK RUN 2026-09-21 (king), which is what moved this off unclassified-not-checked. GEO holds 760 human bone-marrow single-cell RNA-seq DataSets (query: "Homo sapiens"[Organism] AND "bone marrow"[All Fields] AND ("single cell" OR "scRNA-seq")[All Fields] AND "expression profiling by high throughput sequencing"[DataSet Type]; translation recorded, ran clean). GSE120221 was verified individually: 25 samples, Homo sapiens, human bone marrow by scRNA-seq with matched mass and flow cytometry. WHAT THAT DATA CAN SETTLE: which haematopoietic populations express ASH2L and whether its expression tracks a state such as HSC quiescence versus cycling - the associative placement this entry's own literature queries were looking for. WHAT IT CANNOT: function. A functional placement needs perturbation in the state, and that remains never-measured. So the entry is split - the descriptive half is a desk job on deposited data, the functional half still needs an experiment.
absence class assigned2026-09-21 (cycle 47, king)
full texts opened
[
  "32021283 (PMC6969701, 27,316 chars) - absence held"
]
known but unreadable
[
  "31870784 - no PMCID by Europe PMC core or efetch"
]
cell state clause terms
[
  "quiescence",
  "quiescent",
  "dormancy",
  "dormant",
  "drug-tolerant",
  "drug tolerant",
  "persister",
  "persisters",
  "leukemia stem cell",
  "leukemia stem cells",
  "leukaemia stem cell",
  "leukaemia stem cells",
  "self-renewal",
  "self renewal",
  "differentiation block",
  "differentiation arrest",
  "minimal residual disease",
  "measurable residual disease"
]
archive checked
{
  "archive": "GEO DataSets",
  "date": "2026-09-21",
  "datasets_matching": 760,
  "verified_example": "GSE120221 (25 samples, Homo sapiens, human bone marrow scRNA-seq)",
  "closes_the_descriptive_half": true,
  "closes_the_functional_half": false
}
How this could bite us back
  • A WRAD-directed intervention has no dependency support in the index disease, and the one measurement available points the wrong way.
  • ASH2L's residue numbering carries a documented 94-residue offset between the 534-residue isoform used in the literature and UniProt Q9UBL3's 628, so any structure-guided design here inherits that trap.
Still open
  1. Does the WRAD module matter for the FUSION at all, as opposed to for wild-type KMT2A? This graph already carries an absence entry on the lack of any proximity-degron or CRISPR study of WRAD in KMT2A-fusion leukaemia.
  2. Is the positive DepMap contrast for ASH2L reproducible in a larger KMT2A-rearranged panel, and if so what does it mean?
Every source behind this entry (3)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    A bounded PubMed query pairing ASH2L and its aliases with an eighteen-term cell-state clause and a leukaemia clause returns 1 record, a mouse embryonic-stem-cell study; the gene clause alone returns 322 and the state clause alone 96,743.

    NCBI PubMed E-utilities esearch, db=pubmed, queried 2026-09-20 · NCBI Entrez Programming Utilities 2026
    What this evidence cannot show

    Bounded by titles and abstracts; supporting figures not searched beyond the one full text opened. Counts as of 2026-09-20.

    Evidence that argues against this (1)
    • ASH2L is not unstudied in leukaemia: PMID 32021283 shows ASH2L-promoted HOXC8 expression in MLL-rearranged acute leukaemia. The absence is specifically of a CELL-STATE measurement, not of leukaemia work, and an entry that blurred the two would be wrong. Wu YJ et al. 2020
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    The full text of the principal ASH2L leukaemia paper contains no cell-state measurement; its only cell-state word occurs inside a reference title.

    PMID 32021283DOI
    What this evidence cannot show

    One paper. Read via PMC6969701 on 2026-09-20, 27,316 characters after tag stripping. A second candidate (PMID 31870784) was unreadable by all PMC routes and is logged as known-but-unreadable rather than counted.

    Evidence that argues against this (1)
    • PUBLISHED CONFLICTING RESULT: a differentiation-state result for the complex ASH2L belongs to exists and is unreachable from the symbol ASH2L. Cao et al. characterised MM-401, which inhibits MLL1 by blocking the MLL1-WDR5 interaction and therefore the assembly of the very WRAD complex ASH2L is part of, and found that it specifically blocks proliferation of MLL cells by inducing cell-cycle arrest, apoptosis and MYELOID DIFFERENTIATION, without general toxicity to normal bone marrow or non-MLL cells, with transcriptome changes matching MLL1 deletion. That is a class-3 'maintains a state' result obtained by disabling ASH2L's complex - the complex form this beat's rule-64 discipline requires, run on the interface rather than on the subunit name. Cao F et al. 2014
  3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    In DepMap fetched 2026-09-20, ASH2L is depleted below -0.5 in 21.1% of 1,258 screened lines (mean -0.332) and its mean across eleven KMT2A-rearranged lines is -0.175, i.e. +0.157 relative to all lines.

    What this evidence cannot show

    Not floor-compressed, so the positive contrast is interpretable rather than an artefact of the floor - which is what makes it worth recording. Eleven KMT2A-rearranged lines, so the arm mean is not precise. Cancer lines in culture.

    Evidence that argues against this (1)
    • NAMED METHODOLOGICAL DEFEATER for reading +0.157 as 'the KMT2A-rearranged arm needs ASH2L LESS'. Alicea-Velazquez et al. showed that the WDR5-Win motif interaction, and therefore WRAD assembly, is shared across ALL members of the human SET1 family, and that disrupting it severely disrupts MLL1 and SETD1A complexes while only modestly disrupting MLL2/4 and SETD1B. ASH2L is a subunit of every one of those complexes. A whole-gene ASH2L knockout therefore removes six methyltransferase complexes simultaneously and its fitness effect is a sum over them, dominated by whichever is most load-bearing in that line. The number is interpretable as a statement about SET1-family H3K4 machinery in aggregate and is not interpretable as a statement about the MLL1 core complex in KMT2A-rearranged cells, which is what the title claims. `gene-ash2l` in `interactome2/` reaches the same place from the other side: ASH2L has DPY30's essentiality profile and none of its co-dependency signal. Alicea-Velázquez NL et al. 2016
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