Oncofusion

start / graph / absence-no-kmt2a-mllt1-analysis-stratified-by-reciprocal-or-spliced-status

Explainermoderate confidence 3 of 5: One strong study, or several smaller consistent ones.Q26-mllt1-control-arm

Nobody has ever stratified any KMT2A::MLLT1 outcome or drug-response analysis by reciprocal or spliced status - a measured absence, with the queries

also called bounded absence: MLLT1 reciprocal stratification · spliced-status stratification gap

The comparison this whole beat is about has never been run, and this entry records the exact searches that establish it rather than just asserting it. One related study exists, but it pools every partner gene together, which is the confound the comparison was meant to remove.

The same thing, for a scientist

Searches run on PubMed on 2026-09-19, with `querytranslation` read for every zero and every surprising count, return **no study of any kind - clinical or preclinical - that stratifies a KMT2A::MLLT1 outcome, transcriptome or drug response by reciprocal-fusion status or by spliced-fusion status.** The nearest neighbours are three: a pooled-partner paediatric prognostic study [E1]; the Marschalek series on reciprocal fusions, which has exactly two instalments, t(4;11) and t(6;11), and no t(11;19) one [E2]; and a t(4;11) knockdown study [E3]. The spliced-fusion literature for this partner consists of one 2007 molecular letter [E4] with nothing downstream.

Go deeper
The queries, verbatim, with counts and translations
querycountnote
MLLT1 AND reciprocal6ids 27282883, 23628958, 22846743, 19262598, 16433901, 8527389 - all cytogenetic/recombinome descriptions or single cases; none stratifies an endpoint
(MLLT1 OR "MLL-ENL" OR LTG19 OR YEATS1) AND (reciprocal OR spliced) AND (outcome OR survival OR prognosis OR response)6ids 32766858, 24602728, 23628958, 22846743, 12651265, 8180386 - none is a stratified analysis
(MLL-ENL OR "KMT2A::MLLT1") AND (reciprocal OR "ENL-MLL")15mouse translocator models, RT-PCR panels, one 1995 case
reciprocal AND fusion AND (menin OR revumenib OR ziftomenib OR bleximenib OR enzomenib)1PMID 42371796, a JUND/menin-MLL paper, off-topic
KMT2A AND reciprocal AND (menin inhibitor)1same record
"11;19" AND reciprocal44reviewed; cytogenetics and salivary-gland t(11;19), no stratified endpoint
"spliced fusion" AND leukemia0phrase honoured: "spliced fusion"[All Fields] AND (...)

All counts were taken with retmode=json and the querytranslation field inspected.

A PubMed trap this beat hit, which the standing rules do not yet cover

A quoted phrase that PubMed does not hold in its phrase index is silently abandoned and re-mapped to a MeSH-expanded OR query. Measured here:

"spliced fusion"  AND leukemia  -> count 0
    qt: "spliced fusion"[All Fields] AND (...)          phrase honoured
"spliced fusions" AND leukemia  -> count 567
    qt: ("rna splicing"[MeSH Terms] OR ("rna"[All Fields] AND
         "splicing"[All Fields]) OR ... OR "spliced"[All Fields] ...)
                                                        phrase ABANDONED

The singular is a real bounded zero. The plural is not a 567-fold richer literature; it is a different query that PubMed wrote. The brief already warns that singular and plural are different [tiab] queries; this is the sharper version - quoting does not guarantee phrase matching, and the failure is visible only in querytranslation. A beat that ran the plural and reported '567 records on spliced fusions in leukaemia' would be reporting on RNA splicing in general.

The one study that is close, and why it does not close the question

In 90 paediatric MLL-rearranged acute leukaemia patients, 37.8% (34/90) had a single direct MLL fusion gene, 15.6% (14/90) a single reciprocal fusion and 27.8% (25/90) both reciprocal alleles; children with reciprocal MLL fusions had relatively favourable outcomes against children with complex translocations or a single direct allele, 66.1% versus 24.6% and 27.6%, P = 0.001 1. This is, as far as these searches reach, the only clinical outcome analysis in the literature stratified by reciprocal-fusion status. It pools every partner gene, so partner identity and reciprocal status are confounded - and partner identity is itself prognostic and lineage-dependent in this disease. It is chemotherapy-era, n = 77 treated, median follow-up 2.5 years, no MLLT1 breakout and no drug-response endpoint. Its direction (reciprocal-positive does better) matches the t(4;11) infant finding, which makes the pooled result consistent with an AFF1-driven signal rather than a general one.

Bounded rejection: what was read and set aside
  • PMID 12781363 and PMID 17906700, the Rabbitts/Forster Cre-loxP Mll-Enl translocator mice. On-topic by title - these are literally reciprocal chromosomal translocations - but they are model-construction papers: neither compares reciprocal-positive with reciprocal-negative animals, because every animal is reciprocal-positive by design. Recorded separately in concept-mouse-mll-enl-models-are-reciprocal-positive-by-construction.
  • PMID 32766858, 'Exploitable metabolic dependencies in MLL-ENL-induced leukemia'. Surfaces in two of the searches above and is a genuine MLL-ENL paper; it is a metabolic-dependency study with no reciprocal or breakpoint stratification.
  • PMID 34489550 and PMID 34354240, the Marschalek 'role of reciprocal fusions in MLL-r acute leukemia' series. A search on the series title returns count 2: the t(4;11) and t(6;11) instalments. There is no t(11;19) instalment, and MLLT1 is the partner with by far the largest reciprocal-negative class.
  • PMID 29384595 and PMID 32991719, partner-stratified AML outcome papers. Both stratify by partner and neither measures reciprocal status; they are cited elsewhere in this graph for the partner question.

What would change the conclusion: any paper reporting outcome, HOXA signature, MRD kinetics or drug response separately for MLLT1 patients with and without a reciprocal allele; or a supplementary table in a recombinome-derived paper that crosses breakpoint class with any endpoint.

Facts and figures
absence typebounded absence plus bounded rejection
date measured2026-09-19
databasePubMed via NCBI esearch, retmode=json, querytranslation inspected
phrase index trap"spliced fusion" AND leukemia returns 0 with the phrase honoured; "spliced fusions" AND leukemia returns 567 because PubMed abandons the phrase and maps to the rna splicing MeSH tree. Quoting does not guarantee phrase matching.
nearest existing studyPMID 29943896, pooled across all KMT2A partners
what would overturnany report of outcome, HOXA signature, MRD kinetics or drug response given separately for KMT2A::MLLT1 patients with and without a reciprocal allele
absence classmeasured-not-reported
absence class basisCohorts with the necessary transcript data exist; nobody has published the stratification.
absence class assigned2026-09-21 (cycle 47, king)
queries
"spliced fusion" AND leuk…0.000"spliced fusion" AND leukemia: 0reciprocal AND fusion AND…1.000reciprocal AND fusion AND (menin OR revumenib OR ziftomenib OR bleximenib OR enzomenib): 1KMT2A AND reciprocal AND …1.000KMT2A AND reciprocal AND (menin inhibitor): 1MLLT1 AND reciprocal6.000MLLT1 AND reciprocal: 6(MLLT1 OR "MLL-ENL" OR LT…6.000(MLLT1 OR "MLL-ENL" OR LTG19 OR YEATS1) AND (reciprocal OR spliced) AND (outcome OR survival OR prognosis OR response): 6(MLL-ENL OR "KMT2A::MLLT1…15.0(MLL-ENL OR "KMT2A::MLLT1") AND (reciprocal OR "ENL-MLL"): 15"11;19" AND reciprocal44.0"11;19" AND reciprocal: 44
queries — the numbers behind the chart
[
  {
    "q": "MLLT1 AND reciprocal",
    "count": 6
  },
  {
    "q": "(MLLT1 OR \"MLL-ENL\" OR LTG19 OR YEATS1) AND (reciprocal OR spliced) AND (outcome OR survival OR prognosis OR response)",
    "count": 6
  },
  {
    "q": "(MLL-ENL OR \"KMT2A::MLLT1\") AND (reciprocal OR \"ENL-MLL\")",
    "count": 15
  },
  {
    "q": "reciprocal AND fusion AND (menin OR revumenib OR ziftomenib OR bleximenib OR enzomenib)",
    "count": 1
  },
  {
    "q": "KMT2A AND reciprocal AND (menin inhibitor)",
    "count": 1
  },
  {
    "q": "\"11;19\" AND reciprocal",
    "count": 44
  },
  {
    "q": "\"spliced fusion\" AND leukemia",
    "count": 0,
    "note": "phrase honoured in querytranslation"
  }
]
aliases searched
[
  "MLLT1",
  "ENL (avoided bare, contaminated)",
  "LTG19",
  "YEATS1",
  "MLL-ENL",
  "ENL-MLL",
  "KMT2A::MLLT1"
]
How this could bite us back
  • A measured absence invites someone to fill it with an underpowered analysis. With 153 against 101 and a binary endpoint, a null result would be a bounded null and must be reported as one; publishing it as 'reciprocal status does not matter' would close a question this small a study cannot close.
Still open
  1. Is the absence a publication gap or a data gap? The breakpoint classes and the outcomes exist in different institutions, and nothing in the published record says whether they have ever been linked.
  2. Would a conference abstract have it? These searches cover PubMed only; ASH and EHA abstracts are not indexed there and are where a negative subgroup analysis would most plausibly have been reported and then dropped.
  3. Does any RNA-seq dataset of KMT2A::MLLT1 patients allow reciprocal status to be called retrospectively? If reciprocal junction reads can be counted in existing TARGET or St. Jude data, the stratification could be done computationally without touching a new sample.
Every source behind this entry (4)
  1. E1moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    In 90 paediatric MLL-rearranged acute leukaemia patients, 37.8% (34/90) displayed a single direct MLL fusion gene, 15.6% (14/90) carried a single reciprocal fusion and 27.8% (25/90) had both reciprocal MLL fusion alleles, and children with reciprocal MLL fusions exhibited relatively favourable outcomes compared with children with complex translocations or a single direct MLL fusion allele (66.1% versus 24.6% and 27.6%, P = 0.001).

    Relatively favorable prognosis for MLL-rearranged childhood acute leukemia with reciprocal translocations. · Yang L, Ding L, Liang J, Chen J, et al. · Pediatr Blood Cancer 2018
    What this evidence cannot show

    Abstract-level reading; Europe PMC gives no open-access full text. Partners are pooled, so this cannot separate reciprocal status from partner identity. Single-centre paediatric cohort, chemotherapy era, n = 77 treated, median follow-up 2.5 years. The three-group comparison contrasts reciprocal-positive against complex translocations AND single-direct cases together, which is not the two-group contrast this beat proposes.

    Evidence that argues against this (1)
    • A functional study in human t(4;11) lines found the reciprocal product dispensable for growth, cell cycle and apoptosis, so a favourable prognosis associated with reciprocal expression is unlikely to be explained by the reciprocal protein doing something the cell needs. Kumar AR et al. 2011
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    The published series titled 'The role of reciprocal fusions in MLL-r acute leukemia' has exactly two instalments, covering the chromosomal translocations t(4;11) and t(6;11); there is no t(11;19) instalment.

    What this evidence cannot show

    Established by a title search returning count 2, run by a delegated worker and consistent with this author's own searches; the PMID, title and DOI of both instalments were independently re-fetched from PubMed esummary on 2026-09-19. A series title search is sensitive to how a paper is titled; an equivalent t(11;19) study published under a different title would be missed by this query alone, though the partner-specific searches above should have caught it.

    Evidence that argues against this (1)
    • The companion t(4;11) instalment exists and is open access, so the absence of a t(11;19) one is a choice of study system by one laboratory rather than a statement that the question is unaskable. Wilhelm A et al. 2021
  3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    Loss of AF4-MLL had no effect on the growth of either RS4;11 or SEMK2-M1 cells, while knockdown of MLL-AF4 significantly inhibited growth of both - a dependency analysis stratified by reciprocal product, performed only in t(4;11).

    t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL. · Kumar AR, Yao Q, Li Q, Sam TA, et al. · Leuk Res 2011
    What this evidence cannot show

    Abstract-level reading. siRNA knockdown in two lines, not a menin inhibitor and not KMT2A::MLLT1. A negative growth phenotype in an established line says little about a product argued to act at leukaemia initiation.

    Evidence that argues against this (1)
    • The recombinome's own discussion argues the opposite direction from the same class of observation: that reciprocal fusion proteins act as chromatin-opening complexes enabling the direct fusion to activate roughly tenfold more target genes, and may be required only for the onset of the pre-leukaemic state. Meyer C et al. 2023
  4. E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    The spliced-fusion mechanism for MLLT1 is described in a single 2007 Leukemia letter, which carries no abstract in PubMed and is not open access.

    What this evidence cannot show

    PARTIALLY UNREADABLE: no PubMed abstract, Europe PMC pmcid null and isOpenAccess N, so PMC routes 2-4 are unavailable; the publisher page serves only the opening three paragraphs and the reference list. Its data were not read and nothing here is claimed about them.

    Evidence that argues against this (1)
    • A second spliced-fusion paper exists for a different partner and is open access, showing the mechanism has been characterised in detail at least once even if not for MLLT1 outcomes. Cerveira N et al. 2010
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