Oncofusion

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

HB11;19 (CVCL_8227) keeps the YEATS domain and expresses both derivative transcripts - so it is the reciprocal-POSITIVE t(11;19) line, and there is no negative one

also called HB1119 · HB(11;19) · CVCL_8227 · ACH-001736

HB11;19 is the other main cell line for this leukaemia, and unlike its rival it keeps the acetyl-reading module that most patients keep. The paper that first described it also reported that it makes messages from both broken chromosomes, which makes it a mirror-image-positive line - and no mirror-image-negative line for this fusion has ever been made.

The same thing, for a scientist

HB11;19 is the second of the two workhorse human KMT2A::MLLT1 lines and it differs from KOPN-8 on the axis that matters: its MLL-ENL fusion protein **contains** the YEATS domain, putting it in the 84.1% class, and it is correspondingly more sensitive to the YEATS inhibitor SGC-iMLLT at 2 uM [E1]. Cellosaurus CVCL_8227 records the line with DepMap identifier ACH-001736, a KMT2A + MLLT1 fusion referenced to the 1992 Cell paper and to an array-CGH study, homozygous CDKN2A p.Arg80Ter and TP53 p.Thr125Met and p.Arg248Trp, and sex and age at derivation both unspecified [E2]. That 1992 paper states that **in a t(11;19)-carrying cell line fusion transcripts are expressed from both derivative chromosomes** [E3]. Reading the two records together, HB11;19 is reciprocal-positive. Its practical importance for this beat is what follows: the two human lines carrying this fusion are one reciprocal-capable-but-unassayed (KOPN-8) and one reciprocal-positive (HB11;19). **There is no reciprocal-negative t(11;19) cell line**, so the natural experiment that exists in 153 patients has no in vitro counterpart.

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The strength of the reciprocal-positive attribution

Two records, neither of which alone is decisive. The 1992 Cell abstract says 'a t(11;19)-carrying cell line' without naming it 3; Cellosaurus attributes HB11;19's fusion to that paper 2. The inference is strong - the paper is the one that discovered KMT2A, it is the reference Cellosaurus gives for this line's fusion, and no other t(11;19) line existed in 1992 - but it is an inference. The Cell 1992 body could not be read: Europe PMC returns pmcid null and isOpenAccess N, so routes 2-4 of the unreadable test have no PMCID and the publisher serves nothing. Confidence is moderate for the attribution and strong for the underlying claim that some t(11;19) line expresses both derivative transcripts.

The line is menin-dependent, strongly

This graph's existing entry line-hb11-19-is-not-kmt2a-aff1 records a DepMap CRISPR MEN1 gene effect of -1.983 for ACH-001736, the strongest of five KMT2A-rearranged lines checked, against -0.463 for the KMT2A::AFF1 line RS4;11. HB11;19 is also one of the KMT2A-r ALL lines in the VTP-50469 (revumenib-lineage) preclinical panel 4. So the one reciprocal-positive KMT2A::MLLT1 line in existence is also the most menin-dependent line in the panel - a coincidence that is either meaningless or is the whole hypothesis, and with n = 1 there is no way to tell.

A retrieval trap: this line is unreachable by name in PubMed

PubMed returns count 0 for the queries HB1119 (querytranslation: HB1119) and HB-1119 (querytranslation: HB-1119), run 2026-09-19. The Cellosaurus synonym list gives HB(11;19), HB11.19, HB 11;19 and HB1119 2, and the semicolon form is unusable as a PubMed term because PubMed parses semicolons and parentheses as syntax rather than text. Any counted-absence claim about work on this line would therefore be an artefact of indexing, not a finding. Papers using it have to be reached through the fusion name or through citing papers.

What a reciprocal-negative t(11;19) line would be worth

The field has no reciprocal-negative t(4;11) line either - RS4;11 and SEMK2-M1 both express MLL-AF4 and AF4-MLL - so every preclinical package in KMT2A-rearranged leukaemia is unstratified in a known direction. A KMT2A::MLLT1 line derived from one of the 153 intergenic-break patients would be the first reciprocal-negative KMT2A-rearranged line of any partner, and it would be partner-matched to HB11;19. Because 50.7% of t(11;19) patients are in that class, such a line may already exist unrecognised among the KOCL and KOPN series, whose breakpoints have never been mapped at this resolution.

Facts and figures
accessionCVCL_8227
accession verifiedfetched from https://api.cellosaurus.org/cell-line/CVCL_8227?format=txt on 2026-09-19; primary name read back as HB11;19
depmap IDACH-001736
fusionKMT2A::MLLT1 (MLL-ENL)
yeats domain in fusiontrue
reciprocal statuspositive (inferred: the 1992 Cell paper reports both derivative transcripts in a t(11;19) line and Cellosaurus references that paper for this line's fusion)
reciprocal status confidencemoderate
sexunspecified
age at derivationunspecified
pubmed retrieval notePubMed returns count 0 for both 'HB1119' and 'HB-1119'; the semicolon form is unusable as a query term. Literature on this line is not reachable by its own name.
field gapno reciprocal-negative t(11;19) cell line exists, and none exists for t(4;11) either
co lesions
[
  "CDKN2A p.Arg80Ter homozygous",
  "TP53 p.Thr125Met",
  "TP53 p.Arg248Trp"
]
How this could bite us back
  • Every in vitro menin-inhibitor result for this fusion comes from a reciprocal-positive or reciprocal-unassayed line, so the preclinical package is unstratified in a known direction. If reciprocal status modifies menin-inhibitor response, no existing cell experiment could have detected it.
  • HB11;19 carries homozygous CDKN2A loss and two TP53 mutations, so apoptotic readouts in this line are measured in a p53-null-like background and will understate any drug whose effect runs through p53.
Still open
  1. Does HB11;19 express a reciprocal MLLT1::KMT2A transcript today? The 1992 observation predates the line's decades of passage, and reciprocal alleles are known to be lost during clonal progression. One RT-PCR would convert a 34-year-old inference into a current fact.
  2. Which of the KOCL/KOPN t(11;19) lines carries an intergenic (ACER1-MLLT1) break? 50.7% of patients do, so on prior probability at least one of the six existing lines should be reciprocal-negative, and mapping their breakpoints is a week of work that would give the field its first reciprocal-negative KMT2A-rearranged line.
  3. Why is HB11;19's MEN1 dependency the strongest in the panel? If reciprocal-positive KMT2A::MLLT1 cells are more menin-dependent, that is the opposite of what the enforceable-remainder hypothesis predicts, and it is currently a single data point.
Every source behind this entry (4)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    Read in full text (PMC11246743): HB1119 cells are driven by MLL-ENL fusion proteins containing the YEATS domain while KOPN8 cells harbour MLL-ENL fusion proteins lacking it, and greater sensitivity to the YEATS inhibitor SGC-iMLLT was detected for HB1119 and MV4;11 at 2 uM, which the authors read as consistent with HB1119's reliance on the YEATS domain present in its driving MLL-ENL fusion protein.

    PMID 36435883DOI
    What this evidence cannot show

    Read via the PMC HTML page after Europe PMC fullTextXML returned HTTP 500 and efetch db=pmc returned HTTP 429. All four human lines were sensitive to 20 uM SGC-iMLLT, which the authors say may be cytotoxic, so the discrimination rests on one lower concentration. The paper makes no statement about reciprocal transcripts in either line.

    Evidence that argues against this (1)
    • MV4;11, a KMT2A::AFF1 line with no ENL YEATS domain in its fusion, was equally sensitive at 2 uM, which the authors attribute to wild-type ENL - so SGC-iMLLT sensitivity does not cleanly report on fusion-borne YEATS. Hu H et al. 2023
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    Cellosaurus accession CVCL_8227 records HB11;19 (synonyms HB(11;19), HB11.19, HB 11;19, HB1119) as a human cancer cell line of unspecified sex and unspecified age, NCIt term 'B acute lymphoblastic leukemia with t(v;11q23.3) MLL rearranged', carrying a KMT2A + MLLT1 gene fusion named KMT2A-MLLT1 / MLL-MLLT1 / MLL-ENL referenced to PubMed 1423624 and PubMed 16523483 and to DepMap ACH-001736, with homozygous CDKN2A p.Arg80Ter and TP53 p.Thr125Met and p.Arg248Trp, and membership of the Cancer Dependency Map project.

    Cellosaurus cell line HB11;19 (CVCL_8227) · Bairoch A, et al.; Cellosaurus · Cellosaurus (SIB) 2026
    What this evidence cannot show

    Fetched by accession 2026-09-19 with the primary name read back. Sex and age at derivation are recorded as unspecified, so this line cannot be assigned to the infant or non-infant subgroup and cannot be used to control for the age confound in this beat. Cellosaurus records no breakpoint or reciprocal-transcript information.

    Evidence that argues against this (1)
    • Cellosaurus citing the 1992 Cell paper for this line's fusion does not establish that the paper's both-derivatives observation was made in this line, and the paper's body is unreadable. Horsley SW et al. 2006
  3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    The paper that identified KMT2A (then HRX) reports that 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.

    PMID 1423624DOI
    What this evidence cannot show

    ABSTRACT ONLY - Europe PMC returns pmcid null and isOpenAccess N so routes 2-4 of the unreadable test cannot be attempted. The abstract does not name the line. Transcript detection in 1992 is not protein detection.

    Evidence that argues against this (1)
    • Reciprocal expression is not universal in this partner: a 1995 T-ALL case had 3'-KMT2A deleted, precluding any reciprocal product. Chervinsky DS et al. 1995
  4. E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    HB11;19 is one of the human KMT2A-rearranged ALL lines (with KOPN8, MV4;11, SEMK2 and RS4;11) in which exposure to the menin inhibitor VTP-50469 produced a concentration-dependent reduction in proliferation, and three of the eight patient-derived xenografts in the same study are B-ALL t(11;19) MLL-ENL models.

    PMID 31821784DOI
    What this evidence cannot show

    Relayed from a full-text reading (PMC7227117) by a delegated worker; PMID, title and DOI independently re-fetched 2026-09-19. The study reports that 6 of 7 additional MLL-ALL PDXs had extended survival on VTP-50469 without naming the non-responder, and three of those seven are MLL-ENL - so whether the single non-responding PDX was an MLL-ENL model is unresolved and would need Figure 6B.

    Evidence that argues against this (1)
    • Preclinical sensitivity in these models did not translate proportionately: in AUGMENT-101's efficacy population the t(11;19) subgroup achieved CR+CRh in 2 of 13 patients (15.4%), below the overall 22.8%. Issa GC et al. 2025
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