Oncofusion

start / graph / ana-t-11-19-cell-line-panel-and-reciprocal-status

Analysisstrong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.Q26-mllt1-control-arm

Every human t(11;19) KMT2A::MLLT1 cell line, with accessions fetched and read back - and not one of them is known to be reciprocal-negative

also called t(11;19) cell line enumeration · KMT2A-MLLT1 line panel · MLL-ENL cell lines

There are seven human cell lines with this fusion. All but one come from babies under a year old, six are B-cell leukaemias and one is a therapy-related myeloid leukaemia from an adult. None has been shown to lack the mirror-image gene, which is the one property this project most needs a line to have.

The same thing, for a scientist

Cellosaurus was queried for `KMT2A-MLLT1` and for `"MLL-ENL"` on 2026-09-19 and every human cancer line returned was then re-fetched **by accession** with the primary name read back, because a prior cycle of this project recorded a cell line accession that resolved to an unrelated endometrial carcinoma. Seven human lines carry the fusion as a patient-derived lesion: **KOPN-8 (CVCL_1866)**, **HB11;19 (CVCL_8227)**, **Kasumi-10 (CVCL_8485)**, **KOCL-33 (CVCL_3991)**, **KOCL-51 (CVCL_6865)**, **KOPN-1 (CVCL_3937)** and **TRL-01 (CVCL_W777)** [E1]. Six are childhood B-ALL lines from patients aged 3-11 months (one of unspecified age); TRL-01 is from a 34-year-old woman with therapy-related AML [E2]. The panel's reciprocal status: **one line is reciprocal-positive by inference (HB11;19), six are unassayed, and none is reciprocal-negative** [E3]. Two engineered non-patient entries also returned - the transduced human cord-blood line M9-ENL1 (CVCL_A8IE) and mouse Picalm-knockout lines - and are excluded here because their fusion is a transgene and they are reciprocal-negative trivially rather than informatively [E1].

Go deeper
The panel, with everything that was checked
lineaccessionsexagediseasefusion sourceYEATS in fusionreciprocal status
KOPN-8CVCL_1866Female3 monthschildhood B-ALLpatientabsent 3unassayed (reciprocal-capable: intra-MLLT1 break)
HB11;19CVCL_8227unspecifiedunspecifiedB-ALL, t(v;11q23.3)patientpresent 3positive (inferred, 1992) 4
Kasumi-10CVCL_8485Female6 monthschildhood B-ALLpatientunknownunassayed
KOCL-33CVCL_3991Female11 monthschildhood B-ALLpatientunknownunassayed
KOCL-51CVCL_6865Male3 monthschildhood B-ALLpatientunknownunassayed
KOPN-1CVCL_3937Female9 monthschildhood B-ALLpatientunknownunassayed
TRL-01CVCL_W777Female34 yearstherapy-related AMLpatientunknown (junction reported at ENL exon 4)unassayed

Every accession in this table was fetched individually from https://api.cellosaurus.org/cell-line/<AC>?format=txt and the ID line read back before the row was written 1.

Why 'unassayed' and not 'unknown to me'

Cellosaurus records no reciprocal-transcript information for any of these lines 1, and the searches recorded in absence-no-kmt2a-mllt1-analysis-stratified-by-reciprocal-or-spliced-status return no paper assaying one. The 1994 RT-PCR survey that used several of these lines and detected chimeric mRNAs in 8 of 9 t(11;19) leukaemias was assaying the direct transcript; reciprocal translocation appears in its abstract only as background to how the fusion arises 5. So the absence is a property of the literature, not of this search.

The prior probability says a reciprocal-negative line is already sitting in a freezer

50.7% of t(11;19) patients have an intergenic ACER1-MLLT1 break and make no reciprocal allele 3. Six of these seven lines are from infants with B-ALL, the modal patient group. If breakpoint class is independent of whether a line was successfully established, the probability that none of six unassayed lines is reciprocal-negative is about 0.5^6, roughly 1.6%. The most likely state of the world is that two or three of KOPN-8, Kasumi-10, KOCL-33, KOCL-51, KOPN-1 and TRL-01 are reciprocal-negative and nobody has looked. KOPN-8 is excluded from that count on a technicality that is itself informative: its fusion lacks the YEATS domain, so its break is downstream of MLLT1 exon 2 and therefore intra-genic and reciprocal-capable 3.

What mapping these breakpoints would give the field

The first reciprocal-negative KMT2A-rearranged cell line of any partner. There is none for t(4;11) either - RS4;11 and SEMK2-M1 both express MLL-AF4 and AF4-MLL - so every preclinical package in this disease is unstratified in a known direction. A reciprocal-negative t(11;19) line paired against HB11;19 would be partner-matched, and against a YEATS-status-matched line would be architecture-matched too. The work is long-distance inverse PCR or targeted sequencing across the MLLT1 locus in six lines: a week, no new patients, no consent.

Bounded rejection: what was returned and set aside
  • M9-ENL1 (CVCL_A8IE) - human umbilical cord blood transduced with a KMT2A-MLLT1 transgene, described as mimicking primary human pro-B ALL. Excluded as a model of transduction, not of the translocation: it carries no der(19) at all, so calling it reciprocal-negative is true and uninformative.
  • PICALM6A/6B/6D (CVCL_B3QV/B3QW/B3QX) - mouse Picalm-knockout embryonic liver cells transduced with KMT2A-MLLT1. Excluded: mouse, transgenic, and the experimental variable is Picalm.
  • IMS-M1 (CVCL_A623) - returned by the KMT2A-MLLT1 query but its fusion is KMT2A-MLLT3. Excluded, and recorded here as the alias-precision failure this query class produces.
  • KARPAS-45, ML-2, MOLM-13, THP-1, MV4;11, SEM, RS4;11 - not returned; other partners. Not investigated further.
Facts and figures
statusrun
result summarySeven human patient-derived t(11;19) KMT2A::MLLT1 cell lines exist. One is reciprocal-positive by inference, six are unassayed, none is known to be reciprocal-negative. On breakpoint-class priors, two or three of the unassayed six are expected to be reciprocal-negative.
reciprocal negative lines0
prior probability none of six is reciprocal negative0.016
inputs
[
  "Cellosaurus API searches for KMT2A-MLLT1 and \"MLL-ENL\"",
  "individual accession fetches for each returned human patient-derived line"
]
lines
[
  {
    "name": "KOPN-8",
    "accession": "CVCL_1866",
    "sex": "Female",
    "age": "3 months",
    "disease": "childhood B-ALL",
    "yeats_in_fusion": false,
    "reciprocal_status": "unassayed (reciprocal-capable)",
    "depmap": "ACH-001106"
  },
  {
    "name": "HB11;19",
    "accession": "CVCL_8227",
    "sex": "unspecified",
    "age": "unspecified",
    "disease": "B-ALL t(v;11q23.3)",
    "yeats_in_fusion": true,
    "reciprocal_status": "positive (inferred)",
    "depmap": "ACH-001736"
  },
  {
    "name": "Kasumi-10",
    "accession": "CVCL_8485",
    "sex": "Female",
    "age": "6 months",
    "disease": "childhood B-ALL",
    "yeats_in_fusion": null,
    "reciprocal_status": "unassayed",
    "co_lesions": [
      "FLT3-ITD"
    ],
    "note": "XXY karyotype from a female patient; JCRB1410"
  },
  {
    "name": "KOCL-33",
    "accession": "CVCL_3991",
    "sex": "Female",
    "age": "11 months",
    "disease": "childhood B-ALL",
    "yeats_in_fusion": null,
    "reciprocal_status": "unassayed"
  },
  {
    "name": "KOCL-51",
    "accession": "CVCL_6865",
    "sex": "Male",
    "age": "3 months",
    "disease": "childhood B-ALL",
    "yeats_in_fusion": null,
    "reciprocal_status": "unassayed"
  },
  {
    "name": "KOPN-1",
    "accession": "CVCL_3937",
    "sex": "Female",
    "age": "9 months",
    "disease": "childhood B-ALL",
    "yeats_in_fusion": null,
    "reciprocal_status": "unassayed",
    "co_lesions": [
      "TP53 p.Arg248Gln"
    ]
  },
  {
    "name": "TRL-01",
    "accession": "CVCL_W777",
    "sex": "Female",
    "age": "34 years",
    "disease": "therapy-related AML",
    "yeats_in_fusion": null,
    "reciprocal_status": "unassayed",
    "note": "stroma-dependent, established by NOG-mouse xenotransplantation; ENL exon 4 junction reported"
  }
]
excluded
[
  {
    "name": "M9-ENL1",
    "accession": "CVCL_A8IE",
    "reason": "transduced human cord blood, transgene not translocation"
  },
  {
    "name": "PICALM6A/6B/6D",
    "accession": "CVCL_B3QV / CVCL_B3QW / CVCL_B3QX",
    "reason": "mouse, transgenic, Picalm-knockout background"
  },
  {
    "name": "IMS-M1",
    "accession": "CVCL_A623",
    "reason": "returned by the query but is KMT2A-MLLT3, not MLLT1"
  }
]
How this could bite us back
  • Every preclinical result for this fusion comes from lines that are reciprocal-positive or reciprocal-unassayed. If the reciprocal product modifies drug response, no existing cell-based experiment in this partner could have detected it, and the same is true for t(4;11).
  • Six of the seven lines are infant B-ALL, and the fusion's adverse clinical reputation comes from paediatric AML. The panel is therefore mismatched to the population in which the drug question is sharpest.
Still open
  1. Which of Kasumi-10, KOCL-33, KOCL-51, KOPN-1 and TRL-01 has an intergenic ACER1-MLLT1 break? Long-distance inverse PCR or targeted sequencing across the locus in five lines would very probably yield the field's first reciprocal-negative KMT2A-rearranged cell line.
  2. Do any of these lines still express a reciprocal transcript after decades of passage? Reciprocal allele loss during clonal progression is documented, and an RT-PCR panel across all seven is a single afternoon.
  3. Is TRL-01's ENL exon-4 junction YEATS-partial? Exon 4 is the last YEATS-coding exon, so an exon-4 junction sits exactly on the boundary between the partial-inclusion (6.0%) and exclusion (9.9%) classes, and this line would be the only model of that architecture.
Every source behind this entry (5)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    A Cellosaurus search for KMT2A-MLLT1 returns 11 entries, of which the human patient-derived cancer lines are HB11;19 (CVCL_8227), Kasumi-10 (CVCL_8485), KOCL-51 (CVCL_6865), KOPN-1 (CVCL_3937), KOCL-33 (CVCL_3991) and KOPN-8 (CVCL_1866), plus the transduced human cord-blood line M9-ENL1 (CVCL_A8IE) and three mouse Picalm-knockout transductants; a search for 'MLL-ENL' additionally returns TRL-01 (CVCL_W777), a female 34-year-old therapy-related AML line. Individual accession fetches confirm KOCL-33 as female 11 months, KOCL-51 as male 3 months and KOPN-1 as female 9 months, all with NCIt terms 'Childhood B acute lymphoblastic leukemia' and 'B acute lymphoblastic leukemia with t(v;11q23.3) MLL rearranged'; none of the seven records carries any reciprocal-transcript annotation.

    What this evidence cannot show

    Queried and each accession re-fetched on 2026-09-19 with the primary ID read back. Cellosaurus completeness is the limiting factor: a line whose fusion has never been annotated there would not be returned, and the 'MLL-ENL' query surfaced TRL-01 that the 'KMT2A-MLLT1' query did not, which shows the annotations are not uniform. The IMS-M1 hit in the KMT2A-MLLT1 result set is a KMT2A-MLLT3 line and was excluded by reading its record.

    Evidence that argues against this (1)
    • Cellosaurus fusion annotations for several of these lines cite panel or survey papers rather than breakpoint-mapping studies, so 'carries KMT2A-MLLT1' is established at gene level and not at junction level for most of the panel. Drexler HG et al. 2004
  2. E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    TRL-01 was established from therapy-related acute myeloid leukaemia with t(11;19) by xenotransplantation into NOD/SCID IL-2Rgamma-null mice; it is CD13, CD33, CD11a, CD18, CD29, CD49d, CD49e, CD54, CD62L and CD117 positive and CD3, CD4, CD8, CD19, CD34, CD41a, CD41b, CD135 and myeloperoxidase negative; and the translocation in both the original sample and the line generated MLL-ENL chimeric transcripts joining exon 6 and exon 4, described by the authors as a novel isoform.

    Establishment of a myeloid leukemia cell line, TRL-01, with MLL-ENL fusion gene. · Ninomiya M, Abe A, Yokozawa T, Ozeki K, et al. · Cancer Genet Cytogenet 2006
    What this evidence cannot show

    ABSTRACT ONLY; Europe PMC returns pmcid null and isOpenAccess N. The phrase 'joining exon 6 and exon 4, respectively' is ambiguous in the abstract between an MLL exon 6 to ENL exon 4 junction and two different junctions in sample and line; the body was not read and this entry does not resolve it. The line is stroma-dependent and did not support long-term culture, so it is not a drop-in model.

    Evidence that argues against this (1)
    • Therapy-related KMT2A::MLLT1 was described in 2007 as very rare with a single t-AML case in the literature, so this line represents a subgroup that the 2023 recombinome still counts at only 9 t-AML cases out of 460. Meyer C et al. 2023
  3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    Read in full text (PMC11246743): KOPN8 cells harbour MLL-ENL fusion proteins lacking the YEATS domain while HB1119 cells are driven by MLL-ENL fusion proteins containing it; and of 302 t(11;19) patients, 50.7% (n = 153) harbour genomic breaks 5' upstream of MLLT1 but 3' downstream of ACER1, 33.4% (n = 101) break within MLLT1 intron 1 and 15.9% (n = 48) break downstream of exon 2.

    What this evidence cannot show

    Read via the PMC HTML page after fullTextXML returned HTTP 500 and efetch db=pmc returned HTTP 429. The paper says nothing about reciprocal alleles in any line; the inference that a YEATS-less fusion implies an intra-MLLT1 and therefore reciprocal-capable break is this graph's reasoning from the breakpoint geometry.

    Evidence that argues against this (1)
    • The prior-probability argument assumes breakpoint class is independent of whether a line could be established, which has never been tested; if intergenic breaks were associated with any biological property affecting immortalisation, the six unassayed lines could be systematically non-representative. Iida S et al. 1992
  4. E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    In a t(11;19)-carrying cell line, fusion transcripts are expressed from both derivative chromosomes, the more abundant derivative 11 transcript coding for a chimeric protein containing the AT hook motifs fused to ENL.

    What this evidence cannot show

    Abstract only; no PMCID in Europe PMC, so routes 2-4 of the unreadable test are unavailable. The abstract does not name the line, and the attribution to HB11;19 rests on Cellosaurus citing this paper for that line's fusion.

    Evidence that argues against this (1)
    • Reciprocal alleles can be lost during clonal progression, so a 1992 observation is not a statement about the line as distributed in 2026. Meyer C et al. 2023
  5. E5moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    An RT-PCR survey of 25 leukaemias with 11q23 abnormalities amplified chimeric mRNAs in 6 of 7 leukaemias with t(4;11), 6 of 8 with t(9;11) and 8 of 9 with t(11;19), and found the chimeric mRNAs heterogeneous with differential usage of MLL exons irrespective of partner chromosome.

    What this evidence cannot show

    Abstract only; PubMed returns no DOI for this record and Europe PMC no PMCID. The assay detects DIRECT chimeric transcripts; 'reciprocal translocation' appears in the abstract only as background to how the fusion arises, and no reciprocal transcript assay is described. This paper is a Cellosaurus reference for KOCL-33, KOCL-51 and KOPN-1, which is why it is checked here.

    Evidence that argues against this (1)
    • One of nine t(11;19) cases gave no amplifiable chimeric mRNA, which a partner-specific primer panel would also produce for an unusual junction - so even the direct-transcript detection rate is a property of the primer set rather than of the biology. Fu JF et al. 2007
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