Oncofusion

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Explainerstrong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.Q21-index-fusion-models

ALL-PO (CVCL_1069) — an infant KMT2A::AFF1 line that is already in DepMap and has never been screened

also called ALLPO · AllPO · CVCL_1069 · ACH-002209

ALL-PO is a leukaemia cell line from a four-month-old girl with exactly the fusion this project studies. It is already part of the big cancer cell-line collection that dependency screens draw on — it just has never been put through one.

The same thing, for a scientist

ALL-PO (CVCL_1069, DepMap ACH-002209) was established by Gobbi and colleagues from the bone marrow of a **4-month-old female** with t(4;11) B-ALL and characterised as a model of minimal residual disease in SCID mice. Cellosaurus carries an explicit fusion annotation — `Sequence variation: Gene fusion; AFF1 + KMT2A; Name(s)=KMT2A-AFF1, MLL-AFF1, ALL-1/AF4` — plus TP53 p.Arg248Gln homozygous, Caucasian population, MSS, and `Part of: Cancer Dependency Map project (DepMap) (includes CCLE)`. It has deposited DNA-methylation, whole-exome, drug-screening, quantitative-proteomics, microarray and RNA-seq data. **What it does not have is a CRISPR gene-effect score.** A query of the DepMap essentiality screens exposed through Open Targets for MEN1 returned 1,258 screened cell lines; ACH-002209 is absent, while SEM (ACH-000782), SEMK2 (ACH-001735), RS4;11 (ACH-000874), MV4-11 (ACH-000045) and HB11;19 (ACH-001736) are all present. So the material gap that the standing weak spot describes is, for at least one infant line, a screening gap.

Go deeper
The correction this entry carries

This graph's standing weak spot reads 'Eleven cell lines, none infant-derived, underpin every dependency conclusion.' The second clause is true of the screened panel and false of the collection. ALL-PO is a 4-month-old infant's KMT2A::AFF1 line, it is a CCLE/DepMap line, and it carries omics but no Chronos score 123.

The distinction matters because it changes what the fix is. 'No infant line exists' implies a derivation programme costing years. 'The infant line exists and has not been screened' implies one Avana or Humagne library transduction in a line that is already in the Broad's own collection.

What else the line carries

TP53 p.Arg248Gln homozygous 2. That is a large confound for any DNA-damage, apoptosis or chemosensitivity work, and it is the same codon mutated heterozygously in SEM. Infant KMT2A-rearranged ALL has among the lowest mutation burdens of any cancer and TP53 mutation is rare in it, so a homozygous R248Q line is not representative of the disease at that locus — a point that applies with equal force to SEM, to KOCL-45 (TP53 R273C) and to KOCL-69 (TP53 R181C). A systematic survey found TP53 mutations in B-precursor ALL cell lines linked specifically to translocation type 4.

Facts and figures
accessionCVCL_1069
depmap IDACH-002209
resolved byCellosaurus accession lookup 2026-09-19; primary name read back as ALL-PO; DepMap id taken from the record's DR line
age at derivation4 months
infant derivedtrue
sexFemale
siteBone marrow
lineageB-precursor
fusionKMT2A::AFF1 (Cellosaurus gene-fusion annotation)
msiMSS
in depmap collectiontrue
depmap crispr gene effectfalse
obtainableYes — a CCLE/DepMap collection line; also in the COSMIC cell lines project (Cosmic-CLP 910944)
co lesions
[
  "TP53 p.Arg248Gln homozygous"
]
omics available
[
  "DNA methylation",
  "whole-exome",
  "drug screening",
  "quantitative proteomics",
  "microarray",
  "RNA-seq",
  "SNP array"
]
How this could bite us back
  • Homozygous TP53 R248Q means any apoptosis-dependent or DNA-damage-dependent result in this line is measured in a p53-null background and cannot be transferred to p53-wild-type infant disease.
  • A single screened infant line would be n=1. A dependency present in ALL-PO and absent in SEM would be uninterpretable between 'infant-specific' and 'ALL-PO-specific' without at least two more infant lines.
  • If the infant screening gap is closed and the menin dependency does NOT appear, the graph loses its central instrument for nominating targets in exactly the population it cares about.
Still open
  1. Would a genome-wide CRISPR screen in ALL-PO place MEN1 where SEM and RS4;11 place it? This is the cheapest single experiment that could test whether the graph's dependency picture is age-invariant.
  2. Does the homozygous TP53 R248Q make ALL-PO unusable as a screening line, given that infant KMT2A-rearranged ALL is TP53 wild-type in almost every patient? If so the infant screening gap is wider than one screen.
  3. Why has a DepMap collection line with full omics never been screened? If the reason is growth rate or transduction efficiency, that is a technical obstacle the field should record rather than rediscover.
Every source behind this entry (4)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    ALL-PO was established from a human acute lymphoblastic leukaemia carrying the t(4;11) translocation and was characterised as a model of minimal residual disease in SCID mice.

    PMID 9444945DOI
    What this evidence cannot show

    Title and bibliographic record fetched from PubMed on 2026-09-19; abstract not retrieved in full and the paper was not read. The patient's age is taken from Cellosaurus [E2], not from this paper, so the infant status and this founding report are separately sourced.

    Evidence that argues against this (1)
    • A 1997 SCID-mouse MRD model is a xenograft in a host with residual NK activity and no human niche, which is why the field moved to NSG. Engraftment behaviour reported in that system does not transfer, and the line's usefulness today rests on its genomics rather than on its original in vivo characterisation. Townsend EC et al. 2016
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    Cellosaurus accession CVCL_1069 records ALL-PO as a female human cancer cell line aged 4 months at sampling, derived in situ from bone marrow, with disease terms 'Childhood B acute lymphoblastic leukemia' and 'B acute lymphoblastic leukemia with t(v;11q23.3) MLL rearranged', an explicit KMT2A-AFF1 gene-fusion annotation, a homozygous TP53 p.Arg248Gln mutation, microsatellite-stable status, and membership of the Cancer Dependency Map project (DepMap, including CCLE) under DepMap identifier ACH-002209.

    Cellosaurus cell line ALL-PO (CVCL_1069) · Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
    What this evidence cannot show

    Fetched by accession 2026-09-19. The KMT2A-AFF1 annotation is attributed by Cellosaurus to a review (PMID 14671638) and to a multi-omics profiling paper (PMID 35354797), not to a primary junction-sequencing report. 'Part of DepMap' denotes collection membership and carries no implication that a CRISPR screen was run.

    Evidence that argues against this (1)
    • Cellosaurus's disease term for this line is 'Childhood B acute lymphoblastic leukemia', not the infant term (NCIt C122617) it applies to the Perth lines. So the database's own disease field would not select ALL-PO in an infant-leukaemia query even though its age field says 4 months. Two fields in one record point different ways, and which one an inventory keys on decides whether infant material appears to exist. Leo IR et al. 2022
  3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    ALL-PO (ACH-002209) has no DepMap CRISPR gene-effect measurement: a query of DepMap essentiality screens for MEN1 through the Open Targets Platform GraphQL API on 2026-09-19 returned gene-effect values for 1,258 cell lines, and ACH-002209 was not among them, whereas SEM (ACH-000782, -0.959), SEMK2 (ACH-001735, -1.667), RS4;11 (ACH-000874, -0.463), MV4-11 (ACH-000045, -1.198) and HB11;19 (ACH-001736, -1.983) all returned values.

    DepMap CRISPR (Chronos) gene-effect screens for MEN1 (ENSG00000133895), queried via the Open Targets Platform GraphQL API · Broad Institute Cancer Dependency Map; Open Targets Platform · Open Targets Platform / DepMap 2026
    What this evidence cannot show

    Absence from one gene's screen list is strong but not conclusive evidence of absence from the screen collection: a line could in principle be screened and have a missing value for one gene. The 1,258-line count is the number returned for MEN1 in this API release, which lags the DepMap portal; a newer DepMap release could have added the line. The positive controls are the load-bearing part — five expected lines all returned values from the same call.

    Evidence that argues against this (1)
    • The MEN1 values themselves undercut a simple reading of the panel. HB11;19, a KMT2A::MLLT1 line, is the most menin-dependent of the five at -1.983, more than twice the effect in SEM and four times that in RS4;11 — so within this panel the strength of menin dependency does not track the index fusion, and adding one infant KMT2A::AFF1 line would not by itself resolve a fusion-versus-line question. Broad Institute Cancer Dependency Map; Open Targets Platform 2026
  4. E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    TP53 mutation frequency in B-precursor acute lymphoblastic leukaemia cell lines is specifically linked to the type of chromosomal translocation the line carries, so a TP53 mutation in a t(4;11) line is a property of the line population rather than of the patient population.

    PMID 20575032DOI
    What this evidence cannot show

    Bibliographic record fetched 2026-09-19; abstract not read in full and the paper was not read. The claim as stated is the paper's title proposition; the direction and magnitude of the linkage by translocation type are not established here and should not be quoted from this entry.

    Evidence that argues against this (1)
    • An alternative and simpler explanation is selection during immortalisation rather than any translocation-specific mechanism: TP53 loss is a general enabler of continuous culture, and lines from low-mutation-burden leukaemias would be the ones most in need of it. That explanation predicts the same observation without any fusion-specific claim. Drexler HG et al. 2004
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