Oncofusion

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Mechanismmoderate confidence 3 of 5: One strong study, or several smaller consistent ones.Q60-cellstate2

AF10/MLLT10 fusions drive aberrant self-renewal of non-stem progenitors — found only by opening the paper

also called AF10 self-renewal · CALM-AF10 MOZ/ENL

Fusions involving the AF10 gene make ordinary blood progenitor cells behave like stem cells that renew themselves forever. The paper showing this has a title that mentions none of that, so a keyword search misses it.

The same thing, for a scientist

AF10 fusion proteins — CALM::MLLT10 in the experiments shown — cause aberrant SELF-RENEWAL of non-stem haematopoietic progenitors, and the interaction of ENL with the MOZ/MORF lysine acetyltransferases, via the ENL YEATS domain, is critical for CALM-AF10-mediated transformation [E1]. This is the only cell-state result for MLLT10 in the literature, and the bounded query for this beat found it and a title check threw it away [E2]. In DepMap, whole-gene MLLT10 loss has no effect anywhere: 0.6% of 1,258 lines depleted, KMT2A-rearranged mean -0.096 [E3].

Go deeper
The retrieval failure, stated precisely

The bounded query returned 29 records. Twenty-eight are measurable-residual-disease monitoring of KMT2A::MLLT10 and PICALM::MLLT10 transcripts, cytogenetic risk stratification, and fusion-detection method papers — MLLT10 appearing as an RT-PCR or ddPCR target. The twenty-ninth is PMID 37031220, whose title is 'MOZ/ENL complex is a recruiting factor of leukemic AF10 fusion proteins'.

On title alone that reads as a recruitment paper, and it was scored off topic. The full text (PMC10082848, 73,027 characters, opened 2026-09-20) contains nine occurrences of self-renewal and three of colony-forming, and states the self-renewal result in its opening sentence 1.

A count of 29 reads as a healthy state literature and is almost entirely diagnostics; a title check on the same 29 returns zero and is wrong. Both numbers mislead in opposite directions.

Why the DepMap null says nothing here

There is no KMT2A::MLLT10 or PICALM::MLLT10 line in the matched panel at all, so the KMT2A-rearranged mean for MLLT10 is computed over lines that do not carry an MLLT10 fusion. It is not a weak test of the fusion context; it is not a test of it 3. The same whole-gene-versus-fusion-allele problem as AFF1, MLLT1 and MLLT3 applies on top.

Facts and figures
genegene-mllt10
uniprotP55197
evidence class3
rule 80 outcomeabsence withdrawn after opening PMC10082848
cell type
{
  "required_in": "no screened line",
  "state_result_system": "murine progenitors with CALM::MLLT10"
}
cell state
{
  "maintains": [
    "cell-state-stem-like-self-renewal"
  ],
  "context": "fusion context, CALM::MLLT10"
}
depmap
{
  "pct_all_lines_depleted": 0.6,
  "mean_all_lines": 0.06,
  "mean_kmt2ar": -0.096,
  "panel_note": "no MLLT10-fusion line in the matched panel"
}
partners named
[
  "ENL/MLLT1",
  "MOZ/KAT6A",
  "MORF/KAT6B",
  "DOT1L"
]
How this could bite us back
  • A MOZ/MORF inhibitor would hit KAT6A, which normal haematopoiesis also needs; the self-renewal it removes may be the healthy kind as well.
  • The route runs through ENL's YEATS domain, which is the same module several other programmes in this graph depend on, so blocking it is not a clean single-mechanism intervention.
  • The result is in CALM::MLLT10 and transferring it to KMT2A::MLLT10 is an untested generalisation across the 5' partner.
Still open
  1. Does KMT2A::MLLT10 drive self-renewal through the same MOZ/ENL route as CALM::MLLT10, or does the KMT2A moiety change the requirement?
  2. Would a MOZ/MORF acetyltransferase inhibitor act on KMT2A-rearranged as well as AF10-rearranged disease? The paper proposes it for AF10 translocations only.
Every source behind this entry (3)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    AF10 (MLLT10) fusion proteins cause aberrant self-renewal of non-stem haematopoietic progenitors via ENL, whose YEATS-domain interaction with MOZ/MORF acetyltransferases is critical for CALM-AF10-mediated leukaemic transformation.

    MOZ/ENL complex is a recruiting factor of leukemic AF10 fusion proteins. · Komata Y, Kanai A, et al. · Nature communications 2023
    PMID 37031220DOI
    What this evidence cannot show

    Murine haematopoietic progenitors carrying CALM::MLLT10 (PICALM::MLLT10), NOT KMT2A::MLLT10 and not human infant B-ALL (brief rule 73). Full text opened and read in this beat via PMC10082848. The self-renewal readout is colony-forming and replating, which measures progenitor potential in vitro.

    Evidence that argues against this (1)
    • The self-renewal is attributed to the AF10 fusion acting through ENL and MOZ, so it is not straightforwardly a property of MLLT10. An ENL-centred reading is equally supported by the same experiments, and this graph should not record the result as a cell-state function of MLLT10 without noting that the necessary partner is a different gene. Takahashi S et al. 2021
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    A bounded PubMed query pairing MLLT10 and its aliases with an eighteen-term cell-state clause and a leukaemia clause returns 29 records; a title-only check scores zero on topic, and opening the one mechanistic record scores one.

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

    Retrieval measurement as of 2026-09-20. The 28 non-mechanistic records are genuinely on the gene and genuinely off the question, which is why the count alone is misleading.

    Evidence that argues against this (1)
    • PUBLISHED CONFLICTING RESULT against 'this is the only cell-state result for MLLT10 in the literature'. A second maintenance result exists and is reachable only through CRM1 and CALM, not through MLLT10 or any of its aliases: Conway et al. show that CRM1 localises to HOXA loci and recruits CALM-AF10 there, and that genetic or pharmacological disruption of the CALM-CRM1 interaction prevents CALM-AF10 enrichment at HOXA chromatin with IMMEDIATE loss of transcription - an ongoing-maintenance result for the same fusion. A bounded query pairing MLLT10 with an eighteen-term cell-state clause cannot reach a paper framed on a nuclear export receptor and a HOXA cluster, so '29 records, title check scores zero, one opened scores one' is a floor on what opening full texts would find, not a measurement of the literature. Conway AE et al. 2015
  3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    In DepMap fetched 2026-09-20, MLLT10 is depleted below -0.5 in 0.6% of 1,258 lines (mean +0.060) and the matched KMT2A-rearranged panel contains no MLLT10-fusion line.

    What this evidence cannot show

    The panel composition is the limitation: with no MLLT10-fusion line present this is not a test of the fusion context. Whole-gene CRISPR in any case cuts both alleles.

    Evidence that argues against this (1)
    • METHODOLOGICAL DEFEATER beyond the panel composition the caveat names. AF10/MLLT10's leukaemic function runs through partners that are themselves multiply redundant: Komata et al. show the MOZ/ENL complex recruits the DOT1L/AF10 fusion complex and maintains its chromatin retention through MOZ/MORF acetyltransferase activity, with ENL's YEATS domain as the critical contact - and Luo et al. showed ENL/MLLT1 and AF9/MLLT3 sit in three distinct SEC-family complexes. A whole-gene MLLT10 knockout in a line with no MLLT10 fusion measures the wild-type protein against that redundancy, which is why +0.060 across 1,258 lines is uninformative in both directions and should not be reported alongside the mechanism as if it qualified it. Komata Y et al. 2023
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