Oncofusion

start / graph / fusion-kmt2a-myo1f

Fusionmoderate confidence 3 of 5: One strong study, or several smaller consistent ones.Q-partners-deferred

KMT2A::MYO1F, t(11;19)(q23;p13.2) — recurrent in infant AML, and never functionally tested

also called MLL-MYO1F · MLL::MYO1F · KMT2A-MYO1F

A rare but repeating leukaemia fusion of babies, joining KMT2A to a small motor protein that crawls along the cell's internal cables. The people who found it pointed out that the motor brings neither of the two things every explanation of this disease relies on — and nobody has tested it since.

The same thing, for a scientist

KMT2A::MYO1F arises from t(11;19)(q23;p13.2) and accounts for 5 patients in the 3401-case recombinome, all AML and 4 of them infants, ranking 22nd among direct partners [E1]. The founding case was an infant acute monocytic leukaemia with a complex translocation involving chromosomes 7, 11, 19 and 22; the fusion protein contains almost the entire MYO1F, and the discovering laboratory stated explicitly that **C-terminal MYO1F has neither the transactivation domain nor the dimerisation domain found in various MLL fusion partners** [E2]. The rearrangement was subsequently reported **recurrent in infant acute myeloid leukaemias** [E3]. Nothing else exists: two PubMed records in total on the intersection, no transformation assay, no mouse model, no cell line, no localisation, no chromatin readout, no menin-inhibitor test [E4]. Together with KMT2A::MLLT11 this is one of two fusions in this beat that their own discoverers flagged as unaccounted for by the field's models and that have never been put into a cell. The partner protein is described in `gene-myo1f`; this entry covers the fusion.

Go deeper
The second unexplained partner

This graph's two mechanistic accounts of KMT2A leukaemia are elongation hijack — the partner brings SEC, P-TEFb or DOT1L — and forced oligomerisation, in which the partner brings only a self-association surface. MYO1F brings neither, by the explicit statement of the report that identified it 2.

That statement deserves the caveat it earns: "neither the transactivation domain nor the dimerisation domain found in various MLL fusion partners" is an argument from the absence of recognised motifs in 2005 annotation. It is not a measurement. The cautionary precedent is GAS7, whose transforming module was called a coiled coil in 2003 and whose self-assembly determinant later turned out to be an F-BAR sheet-forming surface — a module type that motif recognition would not have flagged. MYO1F retains a TH1 membrane-binding tail and an SH3 domain, both interaction modules, and neither has been tested for oligomeric behaviour in the fusion.

So the honest position is symmetrical with KMT2A::MLLT11: a clinically recurrent fusion that might be a counterexample to both models, and that nobody has expressed in a cell in 21 years.

Clinical shape and a diagnosis that may be wrong on the report

Five patients, all AML: 4 infant, 1 paediatric, none adult, none lymphoid 1. The index case was infant acute monocytic leukaemia 2, and the recurrence report is specifically about infant AML 3. This is, by patient distribution, an infant myeloid fusion with no lymphoid presentation on record.

The diagnostic problem is stated by the founding authors: MYO1F is the fourth KMT2A partner at 19p13, and at the cytogenetic level it may be difficult to distinguish MLL-ENL, MLL-ELL, MLL-EEN and MLL-MYO1F fusions created by t(11;19)(q23;p13), so cases of t(11;19) lacking a known fusion gene may result in this gene fusion 2. A t(11;19)(q23;p13) reported as MLL-ENL without transcript typing may be this fusion. That is a live clinical issue, because MLL-ENL is one of the fusions for which menin-inhibitor evidence is strongest and MLL-MYO1F has no evidence at all.

One of the five recombinome cases is a spliced fusion, arising by a truncated 5'-KMT2A recombining upstream of an intact MYO1F rather than by a conventional in-frame junction 1 — relevant because the graph has recently had to correct an over-generalised spliced-fusion figure, and MYO1F's 1-in-5 is a real but tiny denominator.

Cell type, cell state, localization, epigenetics — all absent

Stated flatly rather than padded.

  • Cell type. Infant acute monocytic leukaemia in the index case; infant AML in the recurrent series 23. No experimental cell-of-origin work.
  • Cell state. Not characterised. No differentiation-block phenotype, no replating assay, no transcriptome.
  • Subcellular localization. Not reported for the fusion. Not reported for human MYO1F either, in any source read here.
  • Subnuclear localization. Not reported.
  • Epigenetics. No H3K79 methylation, H3K4 methylation, HOXA-locus occupancy or transcriptome for the fusion or for any MYO1F-rearranged patient sample.
  • Menin. Untested. The fusion retains the KMT2A N-terminus, so menin dependence is predicted and unverified.

The whole entry rests on two case-level publications and one compendium table. It is written because five infants is not nothing and because a reader who encounters a t(11;19) needs to know this partner exists.

Facts and figures
gene5KMT2A
gene3MYO1F
cytobandt(11;19)(q23;p13.2); the index case was a complex translocation involving chromosomes 7, 11, 19 and 22
uniprot5Q03164
uniprot3O00160
uniprot3 verifiedO00160 = MYO1F_HUMAN, PRIMARY gene name MYO1F, 1098 aa, Homo sapiens (UniProt REST, fetched 2026-09-19; primary gene name and length read back from the record, and the length independently matches the 1098 residues predicted in the founding cloning report).
prognosisNot estimable. Five patients, no cohort, no survival data.
PDB noteNo structure of the fusion or of any MYO1F domain.
mechanism class noteDELIBERATELY 'unknown'. The discovering laboratory stated that the retained C-terminal MYO1F has neither a transactivation domain nor a dimerisation domain, and no functional experiment has ever been performed on this fusion. This is the second such case in this beat, with KMT2A::MLLT11.
druggability classunexplored
druggability noteNo menin-inhibitor test, no cell line, no model, no construct in the literature. Clinically, the more pressing issue is that patients with this fusion may be reported as MLL-ENL or MLL-ELL on karyotype alone.
stage of hematopoiesisnot established experimentally; patient phenotype is infant myeloid with monocytic differentiation in the index case
age peakinfancy: 4 of 5 recombinome patients are infants, the fifth paediatric, none adult
subcellular localizationNOT REPORTED, for the fusion or for human wild-type MYO1F in any source read here.
subnuclear localizationNOT REPORTED.
epigenetic readoutNONE PUBLISHED.
cytogenetic ambiguityMYO1F is the fourth KMT2A partner at 19p13; MLL-ENL, MLL-ELL, MLL-EEN and MLL-MYO1F are difficult to distinguish at t(11;19)(q23;p13) without transcript typing.
key interactors notemenin binding is inferred from the retained KMT2A N-terminus and has never been demonstrated for this fusion.
diseases
[
  "infant AML",
  "infant acute monocytic leukaemia",
  "paediatric AML"
]
frequency
{
  "dcal_recombinome_n": 5,
  "dcal_recombinome_rank": 22,
  "dcal_recombinome_total": 3401,
  "infant_aml": 4,
  "paediatric_aml": 1,
  "all_cases": 0,
  "adult_cases": 0,
  "spliced_fusion_cases": "1 of 5"
}
breakpoints
[
  {
    "id": "bp-kmt2a-myo1f-almost-entire-partner",
    "population": "the founding infant acute monocytic leukaemia case: the fusion protein contains almost the entire MYO1F",
    "domains_retained_5": [
      "MBM1",
      "MBM2",
      "AT-hook 1",
      "AT-hook 2",
      "AT-hook 3",
      "SNL1/2",
      "CXXC"
    ],
    "domains_lost_5": [
      "PHD1",
      "PHD2",
      "PHD3",
      "Bromodomain",
      "PHD4",
      "FYRN",
      "TAD",
      "FYRC",
      "WIN",
      "SET"
    ],
    "domains_retained_3": [
      "Myosin motor domain (aa 17-690)",
      "Actin-binding region (aa 579-589)",
      "IQ motif (aa 693-722)",
      "TH1 domain (aa 728-917)",
      "SH3 domain (aa 1041-1098)"
    ],
    "domains_lost_3": [],
    "phenotype_notes": "Exon numbers are omitted for both genes: the source reports 'almost the entire MYO1F' and does not give a junction exon for either partner, and none is inferred. The retained-3 array lists the UniProt canonical domain set on the reasoning that 'almost the entire' partner is retained; this is an inference from the source's wording plus the UniProt map, not a domain-by-domain statement made by the source."
  }
]
PDB IDS
[]
mechanism class
[
  "unknown"
]
drugs
[]
trials
[]
key interactors
[
  "gene-men1"
]
How this could bite us back
  • Because this fusion is cytogenetically indistinguishable from MLL-ENL, MLL-ELL and MLL-EEN, an infant with KMT2A::MYO1F can receive a menin inhibitor on the strength of evidence generated in a different fusion, and a partner-specific failure would be recorded as a t(11;19) non-responder rather than as a signal.
  • If the partner truly supplies no dimerisation surface, then an inhibitor aimed at oligomerisation interfaces has no target here — and the patients it would not help are the ones hardest to identify prospectively.
  • MYO1F is broadly expressed in normal tissue and class-I myosins drive leukocyte motility, so partner-directed inhibition would risk impairing immune-cell migration in already immunocompromised infants.
Still open
  1. Does KMT2A::MYO1F transform haematopoietic progenitors? Never attempted. With KMT2A::MLLT11 it forms a pair of recurrent fusions whose partners were declared to lack both a transactivation domain and a dimerisation domain, and testing either would expose both of the graph's models to falsification for the first time.
  2. Does the retained MYO1F tail self-associate? The 2005 conclusion was drawn from motif recognition, and the SH3 domain and TH1 tail have never been measured for oligomeric state.
  3. How many t(11;19)(q23;p13) cases reported as MLL-ENL, MLL-ELL or MLL-EEN are actually MLL-MYO1F? The founding authors raised this and no cohort has been re-typed.
  4. Does the retained ATP-driven myosin motor do anything in the fusion, or is it inert cargo? No other KMT2A fusion carries a mechanoenzyme.
Every source behind this entry (4)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    In Table 1 of the 3401-patient 2023 KMT2A recombinome, MYO1F is the 22nd-ranked direct translocation partner with 5 patients — 4 infant AML and 1 paediatric AML, with no ALL cases and no adult cases; 1 of those 5 arose by the spliced-fusion mechanism in which a truncated 5'-KMT2A is recombined upstream of an intact partner gene; and the historical partner table places MYO1F at t(11;19)(q23.3;p13.2), 19p13.2, attributed to Lo Nigro et al. (2002), with disease annotation AML.

    The KMT2A recombinome of acute leukemias in 2023. · Meyer C, Larghero P, Almeida Lopes B, Burmeister T, Gröger D, Sutton R, et al. · Leukemia 2023
    PMID 37019990DOI
    What this evidence cannot show

    Read directly from the Europe PMC full-text XML of PMC10169636 with the Table 1 column structure verified from the header. Five patients is a count at which no statement about distribution is stable, and '1 of 5 spliced' is a single case. The paper's AML prose prints the same count as '5x MYOF1', a typographic variant that is not an HGNC symbol.

    Evidence that argues against this (1)
    • The founding report states that MLL-ENL, MLL-ELL, MLL-EEN and MLL-MYO1F are difficult to distinguish cytogenetically at t(11;19)(q23;p13) and that t(11;19) cases lacking a known fusion gene may turn out to be MYO1F, so a referral-based compendium will systematically under-count this partner in favour of the better-known 19p13 fusions. Taki T et al. 2005
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    In an infant acute monocytic leukaemia with a complex translocation involving chromosomes 7, 11, 19 and 22, MLL on 11q23 was fused to MYO1F on 19p13.2-13.3; the MLL-MYO1F fusion protein contains almost the entire MYO1F, however C-terminal MYO1F has neither the transactivation domain nor the dimerisation domain found in various MLL fusion partners; MYO1F is the fourth partner gene of MLL on 19p13, and at the cytogenetic level it may be difficult to distinguish MLL-ENL, MLL-ELL, MLL-EEN and MLL-MYO1F fusions created by t(11;19)(q23;p13), so cases of t(11;19) lacking a known fusion gene may result in this gene fusion.

    PMID 15897884DOI
    What this evidence cannot show

    A single patient with an atypical four-chromosome rearrangement. The 'neither transactivation nor dimerisation domain' claim is an argument from absence of recognised motifs in 2005 annotation, not an experiment: no transformation assay, no reporter assay and no self-association measurement was performed. Read from the abstract.

    Evidence that argues against this (1)
    • Absence of a recognised dimerisation motif is a weak negative in this partner class. GAS7's transforming element was described as a coiled coil in 2003 and later structural work located its self-assembly determinant in F-BAR hydrophilic loops that form two-dimensional sheets — a module motif recognition would not have flagged. MYO1F's retained TH1 tail and SH3 domain are both interaction modules of unmeasured oligomeric behaviour. Hanawa-Suetsugu K et al. 2019
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    The t(11;19)(q23;p13) fusing MLL with MYO1F is recurrent in infant acute myeloid leukaemias.

    The t(11;19)(q23;p13) fusing MLL with MYO1F is recurrent in infant acute myeloid leukemias. · Duhoux FP, Ameye G, Libouton J, Bahloula K, Iossifidis S, Chantrain CF, et al. · Leuk Res 2011
    PMID 21620472DOI
    What this evidence cannot show

    PubMed carries no abstract for this record, so the claim asserted is exactly the title's content: recurrence, infant AML, t(11;19)(q23;p13). Case numbers, breakpoints and outcomes are not asserted. Confidence is moderate for that reason.

    Evidence that argues against this (1)
    • 'Recurrent' amounts to very few cases: the largest systematic series records 5 MYO1F patients in 3401, so recurrence establishes that the fusion is not a singleton without supporting any frequency estimate. Meyer C et al. 2023
  4. E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    No functional, structural, localisation or epigenetic study of KMT2A::MYO1F exists: a PubMed [Title/Abstract] search for (MLL OR KMT2A) AND MYO1F run 2026-09-19 returns exactly 2 records — the 2005 founding case report and the 2011 recurrence report — with both titles read, while the gene-only query MYO1F[Title/Abstract] returns 70 records, none of which concerns the fusion.

    What this evidence cannot show

    A counted-absence claim. MYO1F has no retired HGNC symbol so the septin-style under-count does not apply, but the recombinome prints the symbol as 'MYOF1' in its prose, demonstrating that typographic variants can hide mentions; no search for that variant or for the spelled-out protein name was run. This count supersedes the inherited enumeration's figure of 1 record.

    Evidence that argues against this (1)
    • A literature count cannot bound what has been done: this fusion is cytogenetically indistinguishable from three better-known 19p13 fusions, so experiments performed on material labelled MLL-ENL or MLL-ELL without transcript typing could in principle have included MLL-MYO1F cases without anyone recording it. Taki T et al. 2005
Connected to