In childhood t(11;19), every lymphoblastic case was MLLT1 and every ELL case was myeloid - the one rule that lets an old cohort be de-contaminated
also called ENL versus ELL by lineage · 19p13.3 versus 19p13.1 childhood · Rubnitz 1996 split
Two different genes on chromosome 19 can join to KMT2A and standard chromosome analysis often cannot tell them apart. In children, an RT-PCR study found that all seventeen lymphoblastic cases involved the gene this beat is about, and the only two cases of the other gene were myeloid.
The same thing, for a scientist
MLL is fused to ENL or ELL in leukaemias with t(11;19)(q23;p13), and the two sub-bands - p13.3 and p13.1 - are not always distinguishable by standard cytogenetics. RT-PCR on 26 childhood t(11;19) cases gave: **all 17 ALL cases had MLL/ENL**; of 9 AML cases, 6 had MLL/ENL, 2 had MLL/ELL and 1 had no detectable MLL fusion mRNA [E1]. So in this series ELL involvement was confined to AML and was a minority even there. The 3,401-patient genomic recombinome is consistent at the whole-cohort level: the ELL row is 119 cases with **zero** infant ALL and only 1 adult ALL, against MLLT1's 460 cases of which 404 are ALL [E2]. **The practical consequence is a de-contamination rule with a stated error rate: a childhood *lymphoblastic* t(11;19) can be treated as KMT2A::MLLT1 with high confidence; a *myeloid* t(11;19) cannot.** That rule rescues the lymphoid outcome literature for this partner and leaves the myeloid literature - which is where this partner's adverse reputation comes from - ambiguous [E3].
Where the rule holds and where it breaks
Holds: paediatric and infant ALL series. 0 of 119 ELL cases in the recombinome were infant ALL 2 and 17 of 17 childhood t(11;19) ALL cases were ENL 1. A lymphoid t(11;19) cohort is effectively a KMT2A::MLLT1 cohort.
Breaks: myeloid series, and badly. In 1,256 children with KMT2A-rearranged AML, 19p13.1/KMT2A::ELL was more common than 19p13.3/KMT2A::MLLT1 (75 versus 56), with a further 23 cases recorded at t(11;19)(q23;p13) with no ascertained sub-band 3. A myeloid t(11;19) bucket is a coin flip.
Unknown: adult relapsed/refractory populations, which is exactly what AUGMENT-101's 86%-AML efficacy population is. Neither series speaks to it.
Why this matters for a beat about reciprocal status
The reciprocal-negative arm of KMT2A::MLLT1 is 404/460 lymphoid 2, and lymphoid t(11;19) is almost purely MLLT1 1. So the control-arm population is one in which the partner assignment is reliable even from old cytogenetic records, which is a genuine methodological advantage over trying to run the same analysis in AML. Conversely, any attempt to extend the comparison into the myeloid cases - where this partner is independently adverse and where menin-inhibitor trials recruit - inherits the ELL ambiguity.
| metric | partner gene identity within t(11;19), by lineage |
|---|---|
| value | 17/17 childhood ALL cases were MLL/ENL; 6/9 childhood AML cases were MLL/ENL and 2/9 were MLL/ELL |
| unit | cases |
| population | childhood acute leukaemia with t(11;19) |
| year | 1996 |
| source | PMID 8639852 |
| cohort n | 26 |
| de contamination rule | a childhood LYMPHOBLASTIC t(11;19) can be read as KMT2A::MLLT1; a MYELOID t(11;19) cannot |
supporting large cohort — the numbers behind the chart
{
"recombinome_ELL_total": 119,
"recombinome_ELL_infant_ALL": 0,
"recombinome_ELL_adult_ALL": 1,
"recombinome_MLLT1_total": 460,
"recombinome_MLLT1_ALL": 404
}where the rule fails — the numbers behind the chart
{
"paediatric_AML_ELL": 75,
"paediatric_AML_MLLT1": 56,
"paediatric_AML_unresolved_subband": 23
}- A rule that says 'lymphoid t(11;19) equals MLLT1' will be applied to myeloid cases by anyone who reads only its headline, and in myeloid disease it is close to a coin flip with the two partners carrying opposite risk assignments.
- What is the ELL:MLLT1 ratio in adult relapsed/refractory acute leukaemia? That is the population menin-inhibitor trials recruit, and neither the paediatric AML cohort nor the childhood ALL series speaks to it.
- Would re-testing archived material from historical t(11;19) AML series resolve the sub-band retrospectively? The adverse-risk assignment for this partner rests on cohorts in which a quarter of t(11;19) cases were never sub-banded.
- Does the lineage rule hold in infants specifically, where nearly all the reciprocal-negative arm lives? The recombinome's zero infant-ALL ELL cases suggest yes, but zero in a referral series is a weaker statement than zero in a population.
- E1moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
MLL is fused to ENL or ELL in acute leukaemias containing t(11;19)(q23;p13), and although ENL and ELL localise to bands 19p13.3 and 19p13.1 these breakpoints are not always readily distinguished by standard cytogenetics; in 26 cases of childhood acute leukaemia containing t(11;19) analysed by RT-PCR, all 17 cases of ALL had MLL/ENL fusion transcripts while of the 9 AML cases 6 had MLL/ENL fusions, 2 had MLL/ELL fusions and 1 had no RT-PCR-detectable MLL fusion mRNA; the authors conclude that the majority of 11;19 translocations involve ENL whereas ELL involvement is relatively uncommon in childhood acute leukaemia and may be restricted to AML.
Molecular analysis of t(11;19) breakpoints in childhood acute leukemias. · Rubnitz JE, Behm FG, Curcio-Brint AM, Pinheiro RP, et al. · Blood 1996What this evidence cannot show
ABSTRACT ONLY; PubMed returns no DOI for this 1996 Blood record and Europe PMC no PMCID, so the four PMC routes are unavailable. n = 26, single institution, 1996 RT-PCR with the primer sets of the time - the one case with no detectable fusion may be a junction the primers did not cover rather than a fusion-negative t(11;19). 'ELL may be restricted to AML' is the authors' own hedged wording and is contradicted at larger scale by the ELL row's single adult ALL case in the recombinome.
Evidence that argues against this (1)
- In a much larger paediatric AML cohort, ELL at 19p13.1 is more frequent than MLLT1 at 19p13.3 (75 versus 56), so 'ELL is relatively uncommon' does not hold within the myeloid compartment where the rule matters most. van Weelderen RE et al. 2024
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Read in full text (PMC10169636), Table 1: the ELL row is infant ALL 0 / AML 30 / other 1, paediatric ALL 0 / AML 32 / other 1, adult ALL 1 / AML 51 / other 3, total 119; the MLLT1 row is infant ALL 234 / AML 2 / other 6, paediatric ALL 100 / AML 28 / other 1, adult ALL 66 / AML 16 / other 2, unclassified 4 / 1 / 0, total 460.
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; cell counts read from the flattened Table 1. A molecular referral series: a t(11;19) that was never sent for molecular characterisation appears in neither row, and referral is likely to be more systematic in infant ALL than in adult AML.
Evidence that argues against this (1)
- Referral bias runs in the direction that would produce exactly this pattern: infant ALL is the setting in which KMT2A molecular screening is mandatory, so the near-absence of ELL from the ALL rows partly measures who gets tested. Rubnitz JE et al. 1996
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
In 1,256 children with KMT2A-rearranged AML, 19p13.1/KMT2A::ELL (n = 75) was more frequent than 19p13.3/KMT2A::MLLT1 (n = 56), with 23 further cases recorded as t(11;19)(q23;p13) without an ascertained sub-band; KMT2A::MLLT1 was assigned adverse risk with independent associations with inferior EFS (HR 1.6, P = .01) and higher CIR (HR 1.8, P < .01), while KMT2A::ELL was assigned intermediate risk and was non-significant on EFS, CIR and OS.
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
The abstract statement that 19p13.3/KMT2A::MLLT1 is independently associated with adverse outcomes was read directly by this entry's author; the counts and hazard ratios were relayed from a delegated worker's full-text reading (PMC11225675), with the PMID, title and DOI independently re-fetched from PubMed esummary on 2026-09-19. Paediatric AML only; sub-band ascertainment itself varied across contributing groups, which is why 23 cases remain unresolved.
Evidence that argues against this (1)
- In the lymphoid compartment the ratio reverses completely, so any general statement that 'half of t(11;19) is ELL' is a statement about myeloid disease only. Meyer C et al. 2023
how reliably a t(11;19) record identifies this fusion
the other 19p13 partner, confined to myeloid disease in childhood series
bounds how contaminated an unresolved t(11;19) bucket is, by lineage
- supports →One karyotype band, two partner genes: why t(11;19) and t(10;11) can cancel a real partner effect
a de-contamination rule with a stated failure domain
the control-arm population is 88% lymphoid, where partner assignment is reliable