Who the 460 KMT2A::MLLT1 patients actually are: 88% lymphoblastic, 53% infants, and only 47 cases of AML in the whole series
also called t(11;19)(q23;p13.3) disease distribution · MLLT1 age distribution · recombinome Table 1 MLLT1 row
Of the 460 patients with this fusion in the largest genomic series, nearly nine in ten had lymphoblastic leukaemia and just over half were babies under one year old. Myeloid disease is the minority here - only 47 cases - which matters because the myeloid literature is where this fusion's bad reputation comes from.
The same thing, for a scientist
Table 1 of the 2023 KMT2A recombinome, read in full text, gives the MLLT1 row as: infant ALL 234, infant AML 2, infant other 6; paediatric ALL 100, paediatric AML 28, paediatric other 1; adult ALL 66, adult AML 16, adult other 2; not age classified ALL 4, AML 1, other 0; total 460 [E1]. Collapsing those: **ALL 404 (87.8%), AML 47 (10.2%), other 9 (2.0%)**, and **infant 242 (52.6%), paediatric 129 (28.0%), adult 84 (18.3%), unclassified 5 (1.1%)**. The percentages are this graph's arithmetic on the published counts; the paper prints the counts, not the shares. Two things follow immediately for this beat. First, the 241 spliced (reciprocal-negative) cases are 52.4% of 460 and the infant cases are 52.6% of 460 - nearly the same fraction - and nothing published says whether those are the same patients, overlapping patients or independent groups. If spliced status and infancy are correlated, the partner-matched comparison is confounded by age, which is the single strongest prognostic variable in KMT2A-rearranged disease. Second, the same series records only 10 therapy-induced KMT2A::MLLT1 cases (1 t-ALL, 9 t-AML) [E1], against a 2007 statement that just one t-AML case had then been described [E2] - so the therapy-related subgroup went from n=1 to n=10 in sixteen years and is still too small to analyse.
The numbers, exactly as printed
The overlap nobody has reported, and why it is the first thing to ask for
52.4% of MLLT1 cases are spliced fusions and 52.6% are infants 1. The coincidence is almost certainly just a coincidence, but it cannot be dismissed from published data because the recombinome reports breakpoint class and age separately and never crosses them for this partner. The recombinome does report, for KMT2A breakpoints generally, that infant ALL prefers intron 11 and that the preference switches at about six months of age 1 - and MLLT1 is one of only two partners with a constitutive intron 11 preference 1. That is a KMT2A-side association, not an MLLT1-side one, so it does not settle the question. The 2x2 of spliced-versus-balanced against infant-versus-older is the smallest query that would make the control arm interpretable, and it is one line of SQL against a database that already exists.
Why the lineage split changes how the prognostic literature should be read
The best-known adverse finding for this partner is from paediatric AML, where 19p13.3/KMT2A::MLLT1 is independently associated with adverse outcome in a 1,256-patient international cohort 3. But AML is 10.2% of KMT2A::MLLT1 in the genomic series 1. So the fusion's reputation as high-risk rests on its smallest disease compartment, while its largest - infant and childhood ALL - contains the good-outcome subsets (B-precursor aged 1-9, and T-lineage) 2. This is not a contradiction; it is a statement that lineage, not partner, carries the prognostic signal, and it is consistent with the sign flip already recorded in epi-partner-mllt1-prognostic-sign-flips-between-aml-and-all.
What the denominators are and are not
These are cases referred to one diagnostic centre over twenty years, pre-screened and not pre-screened, characterised by long-distance inverse PCR, multiplex PCR or targeted NGS 1. They are not a population sample. Partner shares reflect who sends samples to Frankfurt and for what reason, and the infant fraction in particular is inflated by the fact that infant ALL is the disease in which KMT2A screening is mandatory. A population incidence for KMT2A::MLLT1 cannot be read off this table and is not given here.
| metric | disease and age distribution of a fusion partner |
|---|---|
| value | 460 |
| unit | patients |
| population | genomically characterised KMT2A::MLLT1 acute leukaemia |
| region | international referrals to the Diagnostic Center of Acute Leukemia, Frankfurt |
| year | 2023 |
| source | KMT2A recombinome 2023, Table 1 |
| derived shares note | Percentages below are this graph's arithmetic on the published counts. |
| all PCT | 87.8 |
| aml PCT | 10.2 |
| other PCT | 2 |
| infant PCT | 52.6 |
| paediatric PCT | 28 |
| adult PCT | 18.3 |
| spliced PCT | 52.4 |
| therapy induced t aml n | 9 |
| therapy induced t all n | 1 |
| partner rank in series | 3 |
cells — the numbers behind the chart
[
{
"age_group": "infant",
"ALL": 234,
"AML": 2,
"other": 6,
"total": 242
},
{
"age_group": "paediatric",
"ALL": 100,
"AML": 28,
"other": 1,
"total": 129
},
{
"age_group": "adult",
"ALL": 66,
"AML": 16,
"other": 2,
"total": 84
},
{
"age_group": "not age classified",
"ALL": 4,
"AML": 1,
"other": 0,
"total": 5
}
]comparator partner totals — the numbers behind the chart
{
"AFF1": 1262,
"MLLT3": 612,
"MLLT1": 460,
"MLLT10": 304,
"AFDN": 138,
"ELL": 119
}- If the reciprocal-negative arm turns out to be predominantly infant, any survival difference attributed to reciprocal status would in fact be the infant penalty, and a therapy stratified on reciprocal status would be stratifying on age by proxy while believing it was stratifying on biology.
- Are spliced fusions and infancy correlated in this partner? 52.4% of cases are spliced and 52.6% are infants, and the cross-tabulation has never been published. Until it is, every reciprocal-status comparison in KMT2A::MLLT1 is potentially an age comparison wearing different clothes.
- Do the 47 AML cases differ in breakpoint class from the 404 ALL cases? The recombinome shows minor-BCR breaks are an ALL-specific feature across all partners, but gives no MLLT1-specific lineage-by-breakpoint table.
- What is the population incidence of KMT2A::MLLT1? Every number in this entry is a referral share; nothing in the literature converts it to cases per million per year by age.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Read in full text (PMC10169636), Table 1 row 3: MLLT1, infant ALL 234 / AML 2 / other 6, paediatric ALL 100 / AML 28 / other 1, adult ALL 66 / AML 16 / other 2, not age classified ALL 4 / AML 1 / other 0, total 460; MLLT1 ranks third among direct translocation partner genes after AFF1 (1,262) and MLLT3 (612); therapy-induced cases include MLLT1 among t-ALL partners and MLLT1 (n = 9) among t-AML partners; about 50% of MLLT1 breakpoints (n = 241) localise upstream of MLLT1 exon 1; MLLT1 and SEPTIN6 preferentially use KMT2A intron 11 while other partners tend to intron 9 or upstream; and in ALL patients the infant group shows a clear preference for KMT2A intron 11 fusions which switches at about six months to a preference for intron 9.
The KMT2A recombinome of acute leukemias in 2023. · Meyer C, Larghero P, Almeida Lopes B, et al. · Leukemia 2023What this evidence cannot show
Read in full text via Europe PMC fullTextXML (body element present, 98,196 characters of flattened text); the twelve cell counts were read from the flattened Table 1. Percentages and row/column totals in this entry are our arithmetic, not printed values. A single diagnostic centre's referral series accumulated 2003-2022, so this is not a population sample and the shares are ascertainment-shaped. 'Other' is not defined per partner in the row and includes MPAL and non-acute diagnoses.
Evidence that argues against this (1)
- A large clinical cohort assembled by karyotype rather than by molecular referral gives a different picture of who has this fusion: in 629 children over 1 year with 11q23/KMT2A-rearranged ALL, t(11;19)(q23;p13.3) accounted for 106 patients (20.0%), a paediatric share far above the 100/460 = 21.7% this table implies only by coincidence of denominators. Attarbaschi A et al. 2023
- E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
The 2007 letter that introduced the spliced-fusion mechanism states, in its openly readable opening section, that MLLT1 accounts for about 5% of all MLL rearrangements, that t(11;19)(q23;p13.3) is identified in lymphoid, myeloid and biphenotypic malignancies, that therapy-related translocations between MLL and MLLT1 are very rare with only one t-AML case then described in the literature, and that two subsets within MLL-MLLT1 seem to have a good prognosis - ALL patients between 1 and 9 years and patients with T-lineage ALL.
Spliced MLL fusions: a novel mechanism to generate functional chimeric MLL-MLLT1 transcripts in t(11;19)(q23;p13.3) leukemia. · Meyer C, Burmeister T, Strehl S, Schneider B, et al. · Leukemia 2007What this evidence cannot show
PARTIALLY UNREADABLE. No abstract in PubMed; Europe PMC returns pmcid null and isOpenAccess N so routes 2-4 have no PMCID. The publisher page returns HTTP 200 and serves the first three paragraphs and the full reference list before the paywall; only that visible portion was read, on 2026-09-19. The '5%' and 'one t-AML case' figures are 2007 statements about the literature of that time and have both been superseded. **Denominator note added 2026-09-20 by the coordinator:** the '~5% of all MLL rearrangements' figure is a share of a reference-laboratory series, whose denominator is samples referred for KMT2A breakpoint characterisation rather than a population. Referral series over-represent cytogenetically difficult, cryptic and therapy-related cases, so a partner's share of that series is not its share of incident disease. The figure is carried here as what the letter states, not as a population frequency.
Evidence that argues against this (1)
- The 2023 recombinome records 9 therapy-induced t-AML cases with MLLT1 plus one t-ALL case, so 'only one t-AML case described' was a statement about 2007 and is not the current position. Meyer C et al. 2023
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
In a retrospective international study of 1,256 children with KMT2A-rearranged AML treated 2005-2016, multivariable analysis confirmed independent associations of 4q21/KMT2A::AFF1, 6q27/KMT2A::AFDN, 10p12/KMT2A::MLLT10, 10p11.2/KMT2A::ABI1 and 19p13.3/KMT2A::MLLT1 with adverse outcomes; five-year event-free survival across 13 KMT2A-r groups ranged from 21.8% to 76.2% (P < .01) and additional cytogenetic aberrations occurred in 46.8% of 1,200 patients with complete karyotypes, correlating with inferior overall survival (56.8% vs 67.9%, P < .01).
Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia. · van Weelderen RE, Harrison CJ, Klein K, Jiang Y, et al. · Blood Adv 2024What this evidence cannot show
Abstract-level reading for the numbers quoted here. The abstract does not print the MLLT1-specific EFS value or its n, so 'independently adverse' is the strongest statement supportable without the full text. Retrospective across many national protocols; reciprocal status, breakpoint class and spliced status were not measured in this cohort and could not have been, since it is a cytogenetic study.
Evidence that argues against this (1)
- In a 20-patient MLL-rearranged AML series, MLLT1 and MLLT3 partners were the ones associated with better benefit from allogeneic transplant, the opposite direction to an adverse-risk assignment. Burillo-Sanz S et al. 2018
disease and age distribution of the 460 genomically characterised cases
242 of 460 KMT2A::MLLT1 cases are infants, 234 of them ALL
- co-occurs with →KMT2A-rearranged acute myeloid leukaemia in children and infants
only 47 of 460 cases are AML, yet AML carries this partner's adverse reputation
supplies the age denominators the control arm must be balanced against
the age distribution that makes the infant gap the important one
- ← analogous toKMT2A::MLLT3 across 612 genotyped patients: myeloid at every age, but 248 of them have ALL, and 157 of those are infants
the same table, the paralogous partner
THE ONE GENUINE DEFECT: its '~5% of all MLL rearrangements' was a population claim quoted from a referral series with no denominator note. Corrected 2026-09-20.