Oncofusion

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Explainerestablished confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.Q21-index-fusion-models

RS4;11 (CVCL_0093) — an ADULT KMT2A::AFF1 line, MSI-high, carrying NSD2 E1099K

also called RS4-11 · RS4:11 · RS(4;11) · RS411 · CVCL_0093 · ACH-000874

RS4;11 is one of the three cell lines almost every KMT2A::AFF1 experiment uses. It came from a thirty-two-year-old woman, and its genome is unstable in a way that infant leukaemia's is not.

The same thing, for a scientist

RS4;11 (CVCL_0093, DepMap ACH-000874, ATCC CRL-1873, DSMZ ACC-508) is one of the three most-used KMT2A::AFF1 models and is derived from the bone marrow of a **32-year-old Caucasian female**. Cellosaurus assigns it the NCIt term *Adult* B acute lymphoblastic leukemia. The fusion is annotated in frame with three supporting references including the founding molecular characterisation of the t(4;11) fusion itself. Its co-lesions are **NSD2 p.Glu1099Lys** and **PIK3CD p.Gly971Arg**, both heterozygous, and CCLE classifies it **MSI-high**. It is a member of the NCI Pediatric Preclinical Testing Program cell-line panel — a paediatric testing panel whose t(4;11) representative is an adult's leukaemia.

Go deeper
The adult line in the paediatric panel

RS4;11 is listed in Cellosaurus as Part of: NCI Pediatric Preclinical Testing Program (PPTP) cell line panel and as Adult B acute lymphoblastic leukemia in the same record 1. Both are correct. The consequence is that a large body of paediatric preclinical testing of t(4;11) biology has been done in an adult's cells, and the provenance is stated plainly in the public record rather than hidden — it simply is not carried forward into the papers that use the line.

This is the clean example of the pattern this graph's provenance beat named: the import is declared at source and lost in transit.

Two co-lesions that change what the line can be used for

NSD2 E1099K is an activating mutation in a H3K36 methyltransferase, shared with SCMC-L1 and KOCL-45 1. Any chromatin claim about the fusion made in RS4;11 has an NSD2 gain-of-function in the background.

PIK3CD G971R sits in the PI3K delta catalytic subunit, the isoform that is leucocyte-restricted and the target of idelalisib. A PI3K-pathway result in RS4;11 is therefore not a clean readout of fusion-driven signalling.

MSI-high 2 carries the same objection set out for SEM, and more strongly: RS4;11 is the higher-instability of the two.

Facts and figures
accessionCVCL_0093
depmap IDACH-000874
resolved byCellosaurus accession lookup 2026-09-19; primary name read back as RS4;11
age at derivation32 years
infant derivedfalse
adult derivedtrue
sexFemale
populationCaucasian
siteBone marrow
disease termAdult B acute lymphoblastic leukemia (NCIt C9143)
fusionKMT2A::AFF1, in frame
msiInstable (MSI-high)
in depmaptrue
depmap crispr gene effecttrue
men1 gene effect-0.463
repositoryATCC CRL-1873; DSMZ ACC-508
obtainableYes — ATCC and DSMZ catalogue line
co lesions
[
  "NSD2 p.Glu1099Lys het",
  "PIK3CD p.Gly971Arg het"
]
panels
[
  "NCI Pediatric Preclinical Testing Program cell line panel",
  "COSMIC cell lines project"
]
How this could bite us back
  • RS4;11's MEN1 gene effect (-0.463) is the weakest of the five KMT2A-rearranged lines checked here, weaker than HB11;19 (-1.983) and SEM (-0.959). If a menin-inhibitor argument is built on this line it is built on the least menin-dependent index-fusion line available.
  • PIK3CD G971R makes this line unsuitable for PI3K-pathway combination work, and PI3K/AKT signalling is an active combination hypothesis in infant KMT2A::AFF1.
  • An MSI-high background generates resistance alleles at a rate the disease does not, so resistance-evolution experiments in RS4;11 will overestimate how readily escape mutants arise.
Still open
  1. How much of this graph's KMT2A::AFF1 mechanism rests on RS4;11 specifically, and how much of that would be restated as adult disease if the provenance were carried forward? The partner-provenance beat measured imports across fusions; it has not measured imports across age within the index fusion.
  2. Does the NSD2 E1099K in RS4;11 alter the fusion's chromatin footprint? Nobody has done the isogenic correction, and three lines in this inventory carry the same allele.
Every source behind this entry (3)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    Cellosaurus accession CVCL_0093 records RS4;11 as a Caucasian female human cancer cell line aged 32 years at sampling, derived in situ from bone marrow, with the NCIt disease term 'Adult B acute lymphoblastic leukemia', an in-frame KMT2A-AFF1 gene fusion, heterozygous NSD2 p.Glu1099Lys and PIK3CD p.Gly971Arg mutations, microsatellite instability classified MSI-high, DepMap identifier ACH-000874, ATCC catalogue CRL-1873, and membership of the NCI Pediatric Preclinical Testing Program cell-line panel.

    Cellosaurus cell line RS4;11 (CVCL_0093) · Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
    What this evidence cannot show

    Fetched by accession 2026-09-19 with the primary name read back. The age field is age at sampling; RS4;11 was established at relapse according to standard descriptions, so the diagnosis age was earlier — but still adult, since the record's disease term is the adult one. Cellosaurus also records a misspelling in COSMIC (RS-E11), a reminder that name-based lookups for this line fail.

    Evidence that argues against this (1)
    • A 32-year-old's t(4;11) leukaemia is a real disease entity and not merely a poor stand-in for the infant one. Adult KMT2A::AFF1 B-ALL exists, has its own outcome profile, and is the population in which menin inhibitors are actually being tested at scale — so RS4;11 is the best-matched model available for a large part of the current clinical programme, and calling it an import is correct only relative to the infant question. Gu Y et al. 1992
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    In the next-generation characterisation of the Cancer Cell Line Encyclopedia, RS4;11 is classified microsatellite instability-high.

    Next-generation characterization of the Cancer Cell Line Encyclopedia · Ghandi M, Huang FW, Jané-Valbuena J, et al. · Nature 2019
    PMID 31068700DOI
    What this evidence cannot show

    The per-line call was read from the Cellosaurus record, which attributes it to this paper and independently to Sanger. The paper was not read and the abstract was not read in full. An MSI-high call from sequence signatures is a classification, not a functional mismatch-repair assay.

    Evidence that argues against this (1)
    • Two independent sources agreeing (CCLE and Sanger) makes the classification robust but does not make it informative about the patient: both assays were run on the same cultured stock, decades after derivation, so concordance measures reproducibility of the call and not its provenance. Iorio F et al. 2016
  3. E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    The KMT2A-AFF1 fusion transcript in t(4;11) acute leukaemia is heterogeneous at the messenger RNA level when assayed by polymerase chain reaction, so the fusion junction present in any given line is a specific variant rather than a canonical one.

    PMID 8358709
    What this evidence cannot show

    Bibliographic record fetched from PubMed on 2026-09-19; this record carries no DOI. The paper was not read and the abstract was not read in full. Cellosaurus cites it as a source for the fusion annotation in RS4;11, MV4-11, B1 and AN4;11, so the same 1993 assay underlies the fusion assignment of four lines in this inventory.

    Evidence that argues against this (1)
    • Junction heterogeneity cuts both ways for a model argument. It means two KMT2A::AFF1 lines may not carry the same protein, which weakens the idea that any one line represents the fusion — but it equally means that matching a line to a patient on 'KMT2A::AFF1' is too coarse a match in the first place, so adding infant lines without sequencing their junctions would not fix the mismatch it is meant to fix. Gu Y et al. 1992
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