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

PER-490 (CVCL_W986) — a KMT2A::AFF1 B-ALL line from a nine-day-old infant

also called PER-490A · CVCL_W986

PER-490 is a leukaemia cell line grown from a baby girl who was diagnosed nine days after she was born. It is the closest thing that exists in a laboratory freezer to the disease this project is about.

The same thing, for a scientist

PER-490 (Cellosaurus CVCL_W986) is a continuous cell line established at the Telethon Kids Institute, Perth, from the bone marrow of a female infant diagnosed with KMT2A-rearranged B-ALL at **9 days of age** — recorded by Cellosaurus as `AG 9D` and by the founding panel's clinical table as 'Age (days) at diagnosis: 9'. The karyotype is 46,X,-X,+1,dic(1;21)(p11.2;q22),t(4;11)(q21;q23), with a subclone carrying an additional t(8;11)(q24;q14); KMT2A break-apart FISH split in 191/200 interphase nuclei and directed metaphase FISH placed 5' KMT2A on der(11)t(4;11), the canonical KMT2A::AFF1 orientation. Immunophenotype is CD19+ (100%), CD24+ (100%), HLA-DR+ (100%), iCD79a+ (88%), CD10-negative (<1%), CD34-negative (<1%), with aberrant myeloid CD13 (99%) and CD15 (99%) — the CD10-negative pro-B phenotype with myeloid co-expression that defines infant t(4;11) disease. Doubling time 72-97 hours. **Cellosaurus carries no gene-fusion sequence-variation record for this line**, which is why a fusion-keyed Cellosaurus query returns SEM, RS4;11 and MV4-11 but not PER-490.

Go deeper
Why this line matters more than its citation count suggests

Every dependency conclusion in this graph rests on lines derived from a 5-year-old (SEM), a 10-year-old with AML (MV4-11) and a 32-year-old adult (RS4;11) 4. PER-490 is from a neonate with the index fusion and the index disease. It has RNA-seq and microarray transcriptomes deposited 2 and has been used in vitro and in vivo in several published preclinical programmes 3.

What it does not have is any published CRISPR or shRNA dependency screen, and it is not in DepMap. So it can test a hypothesis nominated elsewhere; it cannot nominate one.

How it was resolved

By Cellosaurus accession, not by name: https://api.cellosaurus.org/cell-line/CVCL_W986?format=txt, read back on 2026-09-19. The record returns ID PER-490, AG 9D, SX Female, DI NCIt; C122617; Infant acute lymphoblastic leukemia with MLL rearrangement, Derived from site: In situ; Bone marrow. The age and the t(4;11) assignment were then checked independently against the clinical and cytogenetic tables of the founding panel's characterisation paper 1, which give patient P287, female, 9 days at diagnosis, WBC 111.8 x10^9/L, CNS2, and karyotype 46,XX,t(4;11)(q21;q23).

Facts and figures
accessionCVCL_W986
resolved byCellosaurus accession lookup 2026-09-19; primary name read back as PER-490
age at derivation9 days
infant derivedtrue
sexFemale
siteBone marrow
lineageB-lymphoid (pro-B, CD10-negative) with myeloid antigen co-expression
fusionKMT2A::AFF1 (cytogenetic t(4;11)(q21;q23) plus KMT2A break-apart FISH; no AFF1-specific probe reported)
karyotype46,X,-X,+1,dic(1;21)(p11.2;q22),t(4;11)(q21;q23)[18]/46,idem,t(8;11)(q24;q14)[3]
in depmapfalse
crispr screen publishedfalse
source institutionTelethon Kids Institute / Perth Children's Hospital, Western Australia
obtainableBy material transfer agreement from the depositing laboratory; no public catalogue number (not in ATCC, DSMZ or JCRB)
synonyms
[
  "PER-490A"
]
immunophenotype
{
  "CD19": "100%",
  "CD24": "100%",
  "HLA-DR": "100%",
  "iCD79a": "88%",
  "CD10": "<1%",
  "CD34": "<1%",
  "CD13": "99%",
  "CD15": "99%",
  "CD33": "23%"
}
doubling time h
[
  72,
  97
]
How this could bite us back
  • A single neonatal line is one patient. Any dependency found only in PER-490 is indistinguishable from a private feature of that child's leukaemia until a second infant line reproduces it.
  • The line is CD10-negative and CD34-negative, so CD34-based enrichment strategies and CD10-directed reagents developed on older-child ALL will not transfer.
  • Two of the panel's in vivo programmes (carfilzomib, dactinomycin) showed potent in vitro cytotoxicity that did not translate into survival benefit in xenograft, so a hit found in this line in vitro is a hypothesis about mouse survival, not a result.
Still open
  1. Does PER-490 retain the fetal gene-expression programme that distinguishes infant from childhood MLL-AF4 ALL, or has culture selected it away? The fetal-liver CRISPR model defines that programme and the comparison has not been run.
  2. What is the exact KMT2A intron and AFF1 exon at the junction? A sequenced breakpoint would convert a cytogenetic assignment into a molecular one and would let this line be placed on the recombinome's intron distribution.
  3. Would a genome-wide CRISPR screen in PER-490 reproduce the MEN1 dependency seen in SEM and RS4;11, or is the menin dependency of the screened panel partly a property of older-child and adult biology?
Every source behind this entry (4)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    PER-490 was established from patient P287, a female infant diagnosed with KMT2A-rearranged B-ALL at 9 days of age (WBC 111.8 x10^9/L, CNS2), who relapsed in bone marrow at 3 months and died of disease with an overall survival of 4 months; the line's karyotype is 46,X,-X,+1,dic(1;21)(p11.2;q22),t(4;11)(q21;q23) with KMT2A break-apart FISH split in 191 of 200 interphase cells, and its immunophenotype is CD19+/CD24+/HLA-DR+/iCD79a+, CD10-negative and CD34-negative with CD13 and CD15 co-expression.

    Preclinical Evaluation of Carfilzomib for Infant KMT2A-Rearranged Acute Lymphoblastic Leukemia · Cheung LC, de Kraa R, Oommen J, et al. · Frontiers in Oncology 2021
    PMID 33937032DOI
    What this evidence cannot show

    Full text read via PMC (PMC8082024), Tables 1-3, not abstract only. The clinical table is retrospective and single-centre. AFF1 involvement is inferred from the t(4;11)(q21;q23) karyotype and KMT2A break-apart FISH; the paper reports no AFF1-specific probe and no RT-PCR fusion transcript for this line, so the partner assignment is cytogenetic rather than molecular.

    Evidence that argues against this (2)
    • A cytogenetically defined t(4;11) is not the same evidence as a sequenced fusion junction, and this matters for a line that will be used as the index-fusion model. In the same panel the sister line PER-494 carries a three-way t(4;11;7) and the authors state explicitly that 'AFF1, formerly known as AF4 was not demonstrated by FISH analysis' — so at least one line in this panel has an AFF1 assignment the paper itself declines to call demonstrated. Cheung LC et al. 2021
    • Long-term culture changes infant ALL cells. The panel's own transcriptome comparison is the reason to trust it and also the reason to worry: reproducibility of drug-target gene expression between line and matched primary specimen was measured rather than assumed, which implies it could have failed. Cruickshank MN et al. 2017
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    Cellosaurus accession CVCL_W986 records PER-490 as a female human cancer cell line, age at sampling 9 days, derived in situ from bone marrow, disease 'Infant acute lymphoblastic leukemia with MLL rearrangement' (NCIt C122617), with microarray and RNA-seq transcriptomic data and doubling times of 97 h and 72 h; it carries no gene-fusion sequence-variation annotation.

    Cellosaurus cell line PER-490 (CVCL_W986) · Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025
    What this evidence cannot show

    Fetched by accession on 2026-09-19 via api.cellosaurus.org. Cellosaurus ages are as reported by depositors and are sometimes rounded or internally inconsistent — the same database flags exactly that problem for Kid92 (CVCL_A088), where the founding paper's text says 16 years and its Table 1 says 28. Here the 9-day figure agrees with the founding paper's table, which is the check that makes it usable.

    Evidence that argues against this (1)
    • The absence of a fusion annotation in Cellosaurus is a real limit on this record, not a formality. It means this line is invisible to the standard fusion-keyed query, and it means the database offers no independent molecular confirmation of the partner — the t(4;11) assignment rests entirely on the depositing laboratory's cytogenetics. Drexler HG et al. 2004
  3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    PER-490 belongs to an eight-line infant ALL panel generated from primary patient samples and used for high-throughput in vitro drug screening and for in vivo xenograft efficacy testing, so the line is an actively used preclinical model rather than a historical deposit.

    PMID 27443263DOI
    What this evidence cannot show

    Abstract read for this item; the panel membership and per-line identity come from the carfilzomib paper's tables [E1], which were read in full. The abstract does not name individual lines, so attribution of a specific experiment to this specific line is by panel membership, not by the abstract.

    Evidence that argues against this (1)
    • Repeated use is not validation. Two of the panel's published in vivo programmes reported failure: carfilzomib gave no survival advantage as monotherapy or with induction chemotherapy despite nanomolar in vitro IC50s, and dactinomycin gave only a small survival benefit at a dose below its toxicity ceiling. The panel's value is partly that it says no. Chiu SK et al. 2025
  4. E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    The eleven KMT2A-rearranged cell lines carrying DepMap CRISPR gene-effect data, as used by this project's own specificity scan, have recorded ages at derivation of 10Y (MV4-11), 65Y (OCI-AML-2), 1Y (THP-1), 31Y (NOMO-1), 20Y (MOLM-13), 5Y (SEM), 32Y (RS4;11), 20Y (MOLM-14), 37Y (SHI-1), 5Y (SEMK2) and unspecified (HB11;19), so no line in the screened panel is derived from an infant under one year and PER-490 at 9 days is younger than every one of them by an order of magnitude.

    What this evidence cannot show

    Resolved on 2026-09-19 by querying each DepMap ACH identifier against Cellosaurus and reading back the primary line name, so the mapping is accession-to-accession and not name-based. HB11;19 has no recorded age at all, so strictly ten of eleven lines have an age and none of those ten is under one year.

    Evidence that argues against this (1)
    • Age at derivation is not the same as age of the biology. THP-1 was derived from a 1-year-old and is myeloid; PER-490 is from a 9-day-old and is B-lymphoid. If the relevant variable is the developmental origin of the transformed cell rather than the chronological age of the patient, a chronological age table is the wrong instrument — and the fetal-liver CRISPR model exists precisely because the relevant window is prenatal, earlier than any patient-derived line can reach. Rice S et al. 2021
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