Oncofusion

start / graph / line-kopb-26-the-t-9-11-b-all-line-nobody-uses

Explainermoderate confidence 3 of 5: One strong study, or several smaller consistent ones.Q29-mllt3-yeats-loss

KOPB-26 (CVCL_7972): a t(9;11) B-ALL line from a 13-month-old, and the model for 42% of this partner's patients that nobody uses

also called KOPB-26 · KOPB26 · CVCL_7972

Almost everything known about this fusion comes from myeloid cells, yet four in ten of its patients have B-cell leukaemia. A B-cell line with exactly this fusion, from a thirteen-month-old girl, has existed since 1992 and appears in none of the mechanistic literature this project cites.

The same thing, for a scientist

Cellosaurus CVCL_7972, fetched by accession on 2026-09-20 with the primary name read back: KOPB-26, **female, 1 year 1 month**, `NCIt C9140 childhood B acute lymphoblastic leukemia` and `NCIt C80342 B-ALL with t(v;11q23.3) KMT2A rearranged`, derived in situ from peripheral blood, carrying the gene fusion **KMT2A + MLLT3**, plus **NSD2 p.Glu1099Lys heterozygous** and two TP53 variants (p.Pro278Leu and p.Arg283fs) [E1]. Its provenance runs back to a 1992 characterisation of 14 leukaemia and lymphoma lines with 11q23 translocations [E2] and a 1994 RT-PCR survey of chimeric mRNAs in 11q23 leukaemias [E3]; the KMT2A::MLLT3 assignment is credited by Cellosaurus to the 2004 cell-line review [E4]. It is one of **two** human B-ALL lines carrying this fusion, the other being YACL95 (CVCL_D4A3, under 1 year) [E1]. This matters because **248 of 612 genotyped KMT2A::MLLT3 patients have ALL and 157 of those are infants** [E5], while the nine other human lines with this fusion are all myeloid or monocytic. The entry exists to record that the lineage-matched model for the largest patient cell of this partner already exists, has existed for three decades, and is absent from this graph's mechanistic literature.

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The record
fieldvalue
accessionCVCL_7972 (primary name read back: KOPB-26)
sex / ageFemale / 1 year 1 month
diseaseNCIt C9140 childhood B acute lymphoblastic leukemia; NCIt C80342 B-ALL with t(v;11q23.3) KMT2A rearranged; ORDO Orphanet_585918
sitein situ, peripheral blood
fusionKMT2A + MLLT3 (KMT2A-MLLT3, MLL-MLLT3, MLL-AF9)
co-lesionsNSD2 p.Glu1099Lys heterozygous; TP53 p.Pro278Leu; TP53 p.Arg283fs
provenancePubMed 1465024 (1992), 8180386 (1994), 14671638 (2004) and eight later records

All from the Cellosaurus record fetched by accession on 2026-09-20 1.

The NSD2 E1099K is worth flagging: it is a recurrent activating histone-methyltransferase mutation in paediatric ALL and in relapsed disease, so this line is not a clean fusion-only background any more than THP-1 is.

Why the absence matters more than the line does

This beat's epidemiology entry establishes that 42% of genotyped KMT2A::MLLT3 patients have ALL and that infant ALL is the partner's largest single patient cell at 157 cases 5. This beat's cell-line entry establishes that nine of eleven human lines with the fusion are myeloid or monocytic.

So the mechanistic literature on this fusion - the murine granulocyte-macrophage progenitor assay, THP-1, MOLM-13, NOMO-1, Mono-Mac-6 - is lineage-matched to the minority of its patients, and the two lines that match the majority are unused.

Three specific questions this beat raised are answerable in KOPB-26 and have never been asked in any B-lymphoid t(9;11) context:

  1. Is the fusion's chromatin occupancy the same in a B-lymphoid background? Every published MLL-AF9 occupancy map is myeloid.
  2. Is the BCOR contact requirement lineage-dependent? The AF9 E531R result that abolishes leukaemogenesis was obtained in murine myeloid progenitors 6.
  3. Is menin dependence the same? Every MLL-AF9 menin GI50 in this graph is myeloid or murine-myeloid.

None of these needs new material. Both lines are catalogued.

What is not known about it

Honest limits, because a line with a thin record invites over-reading.

  • No breakpoint. Neither KOPB-26's KMT2A intron nor its MLLT3 intron is annotated, so whether its fusion protein is YEATS-negative like 98.4% of patients is an assumption.
  • No reciprocal status. Unassayed, like every line in the t(9;11) panel.
  • Not in DepMap. Unlike THP-1, MOLM-13 and NOMO-1, there is no DepMap cross-reference on the record, so it contributes nothing to this graph's dependency work as things stand.
  • The partner assignment is curatorial. The 1992 and 1994 records predate routine molecular partner assignment, and Cellosaurus credits the KMT2A::MLLT3 call to the 2004 review 4. An RT-PCR survey returns negative for every partner it was not designed around, so a 1994 assignment is weak on its own.

The first of those is the one worth fixing before using the line: a single long-read RNA-seq run would give the junction and settle the YEATS question for the only lineage-appropriate model that exists.

Facts and figures
accessionCVCL_7972
accession verifiedfetched from https://api.cellosaurus.org/cell-line/CVCL_7972?format=txt on 2026-09-20; primary name read back as KOPB-26
fusionKMT2A::MLLT3 (MLL-AF9)
sexFemale
age at derivation1 year 1 month
lineageB-cell precursor ALL
siteperipheral blood
fusion breakpoint publishedfalse
reciprocal statusunassayed
second b all lineYACL95 (CVCL_D4A3), sex unspecified, under 1 year
why it matters248 of 612 genotyped KMT2A::MLLT3 patients have ALL and 157 are infants, while nine of the eleven human lines with this fusion are myeloid or monocytic
appearances in this graph before this cycle0
cheapest next steplong-read RNA-seq of the fusion transcript to establish the MLLT3 junction and therefore the line's YEATS status
co lesions
[
  "NSD2 p.Glu1099Lys heterozygous",
  "TP53 p.Pro278Leu",
  "TP53 p.Arg283fs"
]
How this could bite us back
  • A line carrying NSD2 E1099K and two TP53 lesions is not a clean fusion background; results from it would need an isogenic comparison before being attributed to KMT2A::MLLT3.
  • Using an unauthenticated 1992 line to make a lineage claim about 42% of a partner's patients would be a worse error than the lineage gap it is meant to close; authentication should precede use.
Still open
  1. Where does KOPB-26's fusion break within MLLT3? Without it, the only lineage-appropriate model for this partner cannot be placed on the YEATS distribution.
  2. Is KOPB-26 still distributable, and by whom? The record carries no STR profile and no depositor cross-reference of the kind THP-1 and MOLM-13 carry.
  3. Why has no menin-inhibitor or DOT1L-inhibitor panel included a t(9;11) B-ALL line, when the same panels routinely include t(4;11) and t(11;19) B-ALL lines?
Every source behind this entry (6)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    Cellosaurus CVCL_7972 records KOPB-26 as a female, 1-year-1-month childhood B acute lymphoblastic leukaemia line with t(v;11q23.3) KMT2A rearrangement, derived in situ from peripheral blood, carrying a KMT2A + MLLT3 gene fusion, NSD2 p.Glu1099Lys heterozygous and TP53 p.Pro278Leu and p.Arg283fs; CVCL_D4A3 (YACL95) is a second childhood B-ALL line under 1 year of age with the same fusion.

    Cellosaurus record CVCL_7972 (KOPB-26) · Cellosaurus (SIB) 2026
    What this evidence cannot show

    Fetched by accession on 2026-09-20 with the primary name read back. No breakpoint, reciprocal status or DepMap identifier is annotated. The fusion assignment is curatorial, credited to a 2004 review rather than to a primary molecular characterisation of this line.

    Evidence that argues against this (1)
    • Cellosaurus has no 'Problematic cell line' comment on this record, but absence of a misidentification flag is not authentication; the record carries no STR profile, so the line's identity cannot be verified from the database alone in the way THP-1's can. Drexler HG et al. 2004
  2. E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    KOPB-26 appears in a 1992 phenotypic and genotypic characterisation of 14 leukaemia and lymphoma cell lines with 11q23 translocations.

    PMID 1465024DOI
    What this evidence cannot show

    1992, cytogenetic and phenotypic characterisation that predates molecular partner assignment; cited as provenance for the line's existence and 11q23 status, not for its partner.

    Evidence that argues against this (1)
    • A cytogenetic 11q23 call cannot distinguish MLLT3 from any other 9p partner, and the 2004 review that Cellosaurus credits for the partner call states that of 36 lines with 11q23 translocations only 17 were available for independent confirmation. Drexler HG et al. 2004
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    A 1994 reverse transcriptase-polymerase chain reaction survey detected heterogeneous chimeric mRNAs in leukaemias with 11q23 abnormalities and is one of the records Cellosaurus cites for KOPB-26.

    PMID 8180386
    What this evidence cannot show

    A targeted RT-PCR panel returns negative for every partner it was not designed around, so this is weak evidence about which partner the line carries.

    Evidence that argues against this (1)
    • The same limitation applies to most pre-2000 partner assignments in cell-line catalogues, which is why this entry treats KOPB-26's fusion identity as curatorial rather than measured. Drexler HG et al. 2004
  4. E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.review

    A 2004 review of malignant haematopoietic cell lines as in vitro models for MLL gene alterations reported seven cell lines with t(9;11)(p22;q23) among 36 lines with 11q23 translocations, and independently confirmed the reported alterations in the 17 of those lines available to the authors.

    PMID 14671638DOI
    What this evidence cannot show

    A review, and by construction a snapshot of what was catalogued in 2004; the count of seven t(9;11) lines is lower than the eleven this beat's Cellosaurus sweep returns in 2026. Which of the 17 confirmed lines were the t(9;11) ones is not recoverable from the abstract.

    Evidence that argues against this (1)
    • That only 17 of 36 lines were independently confirmed means a substantial fraction of historical 11q23 line assignments rest on the original reports alone, and KOPB-26 may or may not be among the confirmed set. Iida S et al. 1992
  5. E5established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    Among 3,401 genotyped KMT2A-rearranged patients, KMT2A::MLLT3 accounts for 612 cases of which 258 are ALL, with 157 of those in infants - so 42% of this partner's patients have lymphoblastic rather than myeloid disease.

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

    Read in full text from the PMC HTML page (PMC10169636) on 2026-09-20. A diagnostic referral archive, not a population registry; shares reflect which cases were sent for breakpoint characterisation.

    Evidence that argues against this (1)
    • If referral practice differentially selects lymphoid cases - for example because infant ALL is more routinely genotyped - the 42% figure would overstate the lymphoid share in the underlying population, though it would have to be badly wrong to make the two B-ALL lines unnecessary. Meyer C et al. 2023
  6. E6strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    The AF9 E531R mutation, which selectively disrupts BCOR binding, completely abrogates the ability of MLL-AF9 to cause leukaemia in vivo in murine bone marrow progenitors while leaving colony formation intact and increasing in vitro proliferation.

    BCOR Binding to MLL-AF9 Is Essential for Leukemia via Altered EYA1, SIX, and MYC Activity. · Schmidt CR, Achille NJ, Kuntimaddi A, et al. · Blood Cancer Discov 2020
    PMID 32954361DOI
    What this evidence cannot show

    Murine myeloid progenitors with transplantation; the experiment has no lymphoid arm, which is the point being made here rather than a criticism of the paper.

    Evidence that argues against this (1)
    • A requirement established in myeloid progenitors may not hold in B-lymphoid cells, where the fusion's target programme differs; nothing in the literature tests it, so the lineage generality of the BCOR requirement is assumed. Schmidt CR et al. 2020
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