PER-494 (CVCL_A8JU) — infant t(4;11;7) line, and the one whose AFF1 was never demonstrated
also called CVCL_A8JU
PER-494 comes from an eleven-month-old girl whose leukaemia had a three-way chromosome swap involving chromosomes 4, 11 and 7. It is an infant line with the index fusion, but the partner gene itself was never directly shown to be there.
The same thing, for a scientist
PER-494 (CVCL_A8JU) was established from the diagnostic bone marrow of patient P272, a female infant aged 336 days (11 months) at diagnosis with WBC 317 x10^9/L, CNS1, treated on CCG 1883, who relapsed in marrow at 3 months and died with an overall survival of 5 months. The line's karyotype is a complex three-way rearrangement — der(4), der(7)(11qter->11q23::7p13->7qter), add(8)(q24), der(11)(11pter->11q23::4q21->4qter) — with a split KMT2A signal in 95/100 interphase nuclei and metaphase FISH confirming t(4;11;7) with 5' KMT2A retained on der(11). The founding paper states plainly that **AFF1 was not demonstrated by FISH analysis**. Immunophenotype at derivation is B-lymphoid and CD10-POSITIVE (CD19 100%, CD10 100%, CD24 100%, CD38 98%, iCD79a 73%, HLA-DR 99%), which is unusual for infant t(4;11) and matches the primary sample (CD10 84%). It shares an individual with PER-485 (Cellosaurus OI cross-reference), the relapse line.
The partner assignment is the weak link
This line is routinely counted as KMT2A::AFF1 because it carries a t(4;11). But the rearrangement is three-way, involving 7p, and the authors record that AFF1 itself was not shown by FISH 1. In a three-way translocation the 4q21 material that joins KMT2A need not be AFF1 — and this graph's own partner-provenance work has shown how often an index-fusion label is carried by inference rather than by measurement.
The fix is cheap: RNA-seq or RT-PCR across the junction. Until then this line should be recorded as t(4;11;7), KMT2A 5' retained, AFF1 inferred.
CD10 positivity is a real phenotypic divergence
Infant KMT2A::AFF1 ALL is characteristically CD10-negative pro-B. PER-494 is CD10 100% and its matched primary sample was CD10 84% 1. So this is not a culture artefact; it is a genuinely CD10-positive infant KMT2A-rearranged leukaemia. Any claim that the index disease 'is' CD10-negative should be stated as a frequency, not a definition, and this patient is a counted exception with a line attached.
| accession | CVCL_A8JU |
|---|---|
| resolved by | Cellosaurus accession lookup 2026-09-19; primary name read back as PER-494 |
| age at derivation | 336 days (11 months) |
| infant derived | true |
| sex | Female |
| site | Bone marrow |
| lineage | B-lymphoid, CD10-POSITIVE (atypical for infant t(4;11)) |
| fusion | t(4;11;7) three-way; 5' KMT2A retained on der(11); AFF1 NOT demonstrated by FISH |
| partner assignment | inferred from cytogenetics, not molecularly confirmed |
| same individual as | CVCL_W984 (PER-485, relapse) |
| in depmap | false |
| crispr screen published | false |
| source institution | Telethon Kids Institute, Perth |
- Using this line as an index-fusion model without confirming the junction risks importing a different partner's biology into a KMT2A::AFF1 conclusion — the precise failure mode this graph has already documented at 54% of load-bearing experiments.
- PER-494 and PER-485 are one patient. Any result reproduced 'in two Perth lines' that names these two has been reproduced in one child.
- Is the 4q21 partner in PER-494 actually AFF1? One RNA-seq junction call settles it and would either add a fourth infant KMT2A::AFF1 line or remove one.
- Does the CD10-positive phenotype of this patient predict anything about outcome or about menin-inhibitor sensitivity, or is it an incidental marker?
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
PER-494 was established from patient P272, a female infant 336 days old at diagnosis; its karyotype is a three-way t(4;11;7) with 5' proximal KMT2A remaining on der(11) and 3' distal KMT2A translocating to 7p, with a split KMT2A signal in 95 of 100 interphase cells; the paper records that AFF1, formerly AF4, was not demonstrated by FISH analysis; the line is CD19 100%, CD10 100%, CD24 100%, CD38 98%, HLA-DR 99%, iCD79a 73%, CD34 <1%.
Preclinical Evaluation of Carfilzomib for Infant KMT2A-Rearranged Acute Lymphoblastic Leukemia · Cheung LC, de Kraa R, Oommen J, et al. · Frontiers in Oncology 2021What this evidence cannot show
Full text read via PMC (PMC8082024), Tables 1-3. Karyotyping of the line was performed in 2018, 26 years after the primary sample (1992), and cytogenetic analysis of the primary sample failed for insufficient metaphases — so there is no diagnostic karyotype to compare the line against.
Evidence that argues against this (1)
- That the primary sample's karyotype failed removes the only check that would show whether the line's complex three-way rearrangement was present at diagnosis or acquired in culture over 26 years. Array CGH of fusion-positive leukaemia lines has found cryptic gains and losses that were not in the reported karyotypes, so long-passaged lines accumulate changes that routine banding does not see. Horsley SW et al. 2006
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
Cellosaurus accession CVCL_A8JU records PER-494 as a female human cancer cell line, age at sampling 11 months, derived in situ from bone marrow, disease 'Infant acute lymphoblastic leukemia with MLL rearrangement' (NCIt C122617), and cross-references CVCL_W984 (PER-485) as originating from the same individual.
Cellosaurus cell line PER-494 (CVCL_A8JU) · Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025What this evidence cannot show
Fetched by accession 2026-09-19. Cellosaurus carries no gene-fusion annotation and no omics annotation for this line — it is the thinnest record of the four Perth t(4;11) lines. The 11-month figure is Cellosaurus's rounding of the founding paper's 336 days.
Evidence that argues against this (1)
- The same-individual cross-reference to PER-485 is what makes this pair valuable and is also a counting trap: treating PER-494 and PER-485 as two independent infant KMT2A::AFF1 lines inflates the apparent number of patients, exactly the error this project found in the MOLM-13/MOLM-14 pair in its own DepMap panel. Oncofusion knowledge graph et al. 2026
- related to →KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)
t(4;11;7); AFF1 inferred not demonstrated
derived from an 11-month-old infant at diagnosis
Telethon Kids Institute infant ALL panel
- ← related toPER-485 (CVCL_W984) — the relapse half of a matched infant t(4;11) pair, and it has lost CD19
same individual; relapse and diagnosis lines (Cellosaurus OI)