IMSUTi002-A-2 (CVCL_C9HE) — a doxycycline-inducible KMT2A::AFF1 iPSC line, and the isogenic design nobody in this graph has used
also called IMSUTi002-A-2 · 7F3955-KMT2A-AFF1 · CRIEPIi003-A-2 · CVCL_C9HE
Researchers built a stem cell line from a healthy person in which the leukaemia fusion can be switched on with a drug in the water. The same cells with the switch off are a perfect control.
The same thing, for a scientist
IMSUTi002-A-2 (CVCL_C9HE) is a human induced pluripotent stem cell line carrying a Tet-on cassette that simultaneously induces **KMT2A-AFF1** and EGFP on doxycycline. Its parent, IMSUTi002-A (CVCL_XI76), is a keratinocyte-derived iPSC from a healthy male Japanese donor, so the background is non-malignant and the uninduced state is a true isogenic control. Cellosaurus records the transfected components in full: the AFF1 and KMT2A integrations, eGFP, hygromycin-B 4-O-kinase, Tn10 tetR and a truncated HHV-1 VP16 transactivation domain. This is the only system found in this beat that gives **fusion on/off in one genetic background**, and the only one in which the question 'what does KMT2A::AFF1 do to a human cell' can be asked without a confounding donor, co-lesion or lineage.
What it corrects about the pluripotent-route picture
The documented pluripotent-route failures are (a) MLL-AF4 impairs haemato-endothelial specification in hESCs and (b) MLL-rearranged patient blasts cannot be reprogrammed into iPSCs. Neither failure applies here. This line is engineered forward into a healthy iPSC rather than reprogrammed backward from a leukaemia, and the fusion is held off until the experimenter chooses.
So the correct statement is: no patient-derived iPSC of this disease exists, and an engineered, inducible iPSC of this fusion does — publicly registered, with its construct documented. The entry model-pluripotent-stem-cell-route-mll-af4 has been amended accordingly.
The design this makes available, and its limits
Available: timed induction, so the developmental window in which the fusion acts can be varied rather than assumed; a genuine isogenic control; EGFP-linked expression, so fusion-positive cells can be sorted; and a background with no TP53, CDKN2A, NSD2, FLT3-ITD or MSI lesion — unlike every patient-derived line in this inventory.
Limits: the fusion is expressed from a transgene under a tetracycline-responsive promoter with a VP16-derived transactivator, so the dose is set by doxycycline and not by the endogenous KMT2A locus. Given that this graph now holds direct evidence that fusion dose is a sequence-regulated variable with an RNA-binding-protein brake, an inducible overexpression system bypasses exactly the control layer that matters. The donor is also an adult, and the cell is keratinocyte-derived, so any fetal-programme question has to be reconstructed through directed differentiation rather than inherited.
| accession | CVCL_C9HE |
|---|---|
| resolved by | Cellosaurus accession lookup 2026-09-19; primary name read back as IMSUTi002-A-2 |
| model class | engineered inducible iPSC |
| parent line | CVCL_XI76 (IMSUTi002-A), keratinocyte-derived iPSC, healthy Japanese male donor |
| induction | doxycycline Tet-on; co-induces EGFP |
| fusion | KMT2A::AFF1 transgene |
| isogenic control | same line, uninduced |
| patient derived | false |
| infant derived | false |
| co lesions | none recorded — no TP53, CDKN2A, NSD2, FLT3 or MSI lesion |
| functional phenotype reported | false |
| obtainable | depositing institutions (IMSUT / CRIEPI, Japan); no catalogue cross-reference in Cellosaurus |
- An inducible transgene sets fusion dose externally, bypassing the RNA-binding-protein brake that this graph now holds is a real regulatory layer — so a negative result here could mean the dose was wrong rather than the biology absent.
- The transactivator carries a VP16 activation domain, which is a transcriptional confound in a system whose subject is transcriptional elongation.
- The donor is an adult keratinocyte reprogrammed to pluripotency. Any infant- or fetal-specific property has to be manufactured by differentiation rather than inherited, and this graph has no evidence that directed differentiation reproduces the fetal programme.
- Does inducing KMT2A-AFF1 in this line during directed haematopoietic differentiation produce a pro-B phenotype, or does it obstruct specification as the hESC work predicts? That single experiment decides whether this is a model or a reagent.
- What doxycycline concentration gives fusion protein at the level found in a patient blast? Without that calibration an inducible system reports the biology of a dose nobody has.
- Could the same Tet-on cassette be put into an iPSC differentiated toward a fetal-like programme, giving an inducible fusion in the correct developmental context? That would combine the strengths of this line and the fetal-liver CRISPR model.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
A human induced pluripotent stem cell line harbouring KMT2A-AFF1 (IMSUTi002-A-2) was established with the ability to simultaneously induce doxycycline-dependent expression of KMT2A-AFF1 and EGFP, proposed as a model for understanding infant leukaemia and for risk assessment of leukaemogenesis; KMT2A-AFF1 formed by t(4;11) is observed specifically in infant pro-B acute lymphoblastic leukaemia and is the main driver of leukaemogenesis.
Generation of a human induced pluripotent stem cell line harboring the infant leukemia-associated fusion gene, KMT2A-AFF1 (IMSUTi002-A-2) · Takahashi M · Stem Cell Research 2023What this evidence cannot show
Abstract read; full text not read. This is a short resource report in a cell-line-announcement journal, which is a format with minimal functional characterisation by design. The abstract reports that the line was established and that it can induce the fusion; it does NOT report that induction produces any leukaemic, haematopoietic or differentiation phenotype, and nothing in this entry should be read as saying it does.
Evidence that argues against this (2)
- The same fusion expressed in human embryonic stem cells impairs early hemato-endothelial specification and is insufficient for transformation, so the expected result of inducing KMT2A-AFF1 in a pluripotent cell is an obstruction of blood formation rather than a leukaemia. If that reproduces here, the line's usefulness is confined to timed induction AFTER haematopoietic specification, which is a narrower use than the announcement implies. Bueno C et al. 2012
- Fusion dose is a regulated variable: KHDRBS/Sam68-family RNA-binding proteins translationally repress the MLL-AF4 transcript through AU-rich stall sites, and removing those sites with synonymous mutations makes an otherwise poorly-transforming construct leukaemogenic. A doxycycline-driven transgene sets dose externally and therefore cannot model the endogenous brake — which means an inducible system can produce either a phenotype or none depending on a dial the disease does not have. Okuda H et al. 2022
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
Cellosaurus accession CVCL_C9HE records IMSUTi002-A-2 as a human induced pluripotent stem cell line from a Japanese male donor, derived from skin epidermis keratinocytes via parent line IMSUTi002-A (CVCL_XI76), transfected with a Tet-on system inducing EGFP and the KMT2A-AFF1 fusion protein on doxycycline, with documented integrations of AFF1, KMT2A, eGFP, hygromycin-B 4-O-kinase, Tn10 tetR and a truncated HHV-1 VP16.
Cellosaurus cell line IMSUTi002-A-2 (CVCL_C9HE) · Bairoch A, et al. (SIB Swiss Institute of Bioinformatics) · Cellosaurus 2025What this evidence cannot show
Fetched by accession 2026-09-19 with the primary name read back. The donor's age is recorded as unspecified. The record lists no omics data and no repository catalogue cross-reference, so obtainability rests on contacting the depositing institutions (IMSUT and CRIEPI, Japan).
Evidence that argues against this (1)
- The construct includes a VP16-derived transactivation domain in the tet transactivator. VP16 is a potent heterologous activator and its presence in the same nucleus as a fusion protein whose oncogenic mechanism is transcriptional elongation is a confound specific to this design, not a generic overexpression caveat. Bairoch A et al. 2025
- related to →KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)
doxycycline-inducible KMT2A-AFF1 in a healthy-donor iPSC
- refutes →The pluripotent stem-cell route has failed from both ends, and the failures are informative
corrects 'no iPSC of this fusion exists': an engineered inducible one does