The CD24-positive pre-leukaemic state — what the index fusion makes before it makes leukaemia
also called CD24+ pre-leukaemic state · KMT2A::AFF1 pre-leukaemia
When the KMT2A::AFF1 fusion is switched on at the right stage of development, the cells do not become leukaemia straight away: they first enter a distinct in-between state carrying a surface marker called CD24. That in-between state is a target nobody is aiming at.
The same thing, for a scientist
Ontogeny-specific induction of KMT2A::AFF1 drives development of a distinct CD24-positive pre-leukaemic state [E1]. This is one of very few cell-state characterisations in this beat's worklist that is (a) about the INDEX fusion rather than a murine MLL-AF9 or MLL-ENL proxy and (b) defined by a surface marker, which makes it sortable and therefore experimentally tractable. It sits between `cell-state-fetal-program-retention` and overt leukaemia, and it is the state that `cell-state-neonatal-window-of-transformability` predicts should exist.
Why a surface marker matters more than a signature here
Most cell states in this graph are defined by a transcriptional signature, which means they can only be scored after the fact, in dissociated cells, by sequencing. CD24 is a surface antigen: the state can be sorted alive, transplanted, drugged and re-sorted. Of the twenty-two cell-state-* entries in this graph, few carry that property.
The practical consequence is that this is the pre-leukaemic state most amenable to a limiting-dilution transplant asking whether it is the reservoir the disease re-grows from.
What is not known
Whether the CD24-positive state is necessary — whether every KMT2A::AFF1 leukaemia passes through it — is untested, and the paper establishing it does not claim so. Nor is it known whether the state persists in the patient at diagnosis, or whether it is a transient developmental intermediate that is gone by the time disease is detectable. Both are answerable with existing material.
| state definition | A CD24-positive intermediate arising when KMT2A::AFF1 is induced at a permissive ontogenetic stage, preceding overt leukaemia |
|---|---|
| sortable alive | true |
| location | fetal/neonatal haematopoietic compartment |
| fusion | fusion-kmt2a-aff1 |
markers
[ "CD24" ]
atlas refs
[
{
"label": "ontogeny-specific KMT2A::AFF1 induction",
"pmid": "40646135",
"title": "Ontogeny-specific induction of the KMT2A::AFF1-fusion drives development of a distinct CD24 positive pre-leukemic state.",
"authors": "Calderón AS, Ghazanfari R, Masoumi Z, et al.",
"venue": "Leukemia",
"year": 2025,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
}
]relation to existing entries
{
"cell-state-fetal-program-retention": "the background programme this state arises on",
"cell-state-neonatal-window-of-transformability": "the window during which induction produces this state"
}- A pre-leukaemic state is a target with no patients: by the time a child presents, the state may be gone, and a drug that removes it has no trial population.
- CD24 is broadly expressed on normal B-lineage cells, so a CD24-directed intervention would not be selective for this state; the marker is useful for sorting, not for targeting.
- If the state is transient and non-obligatory, removing it would not prevent the disease.
- Is the CD24-positive state obligatory, or one of several routes to KMT2A::AFF1 leukaemia?
- Does a CD24-positive fusion-positive population exist in human cord blood from newborns who later develop infant ALL? The Guthrie-card and cord-blood cohorts could answer this.
- Is the state menin-inhibitor sensitive? Nothing in the graph tests a pre-leukaemic state against any drug.
- E1moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
Ontogeny-specific induction of the KMT2A::AFF1 fusion drives the development of a distinct CD24-positive pre-leukaemic state.
Ontogeny-specific induction of the KMT2A::AFF1-fusion drives development of a distinct CD24 positive pre-leukemic state. · Calderón AS, Ghazanfari R, et al. · Leukemia 2025What this evidence cannot show
2025 report in Leukemia; the abstract was read in this beat and the full text was not opened, so the surface-marker phenotype is taken from the abstract. The system is an ontogeny-controlled induction model rather than patient material, so whether the state exists in patients is untested.
Evidence that argues against this (1)
- Human cord-blood CD34+ cells carrying the reciprocal AF4-MLL show transiently augmented multilineage engraftment but do NOT initiate leukaemia, so a fusion-positive pre-leukaemic expansion in human cells is not by itself sufficient for disease and a CD24-positive intermediate need not be on the causal path. Prieto C et al. 2017
ontogeny-specific induction of the fusion produces this distinct CD24-positive pre-leukaemic state
the background programme this state arises on
the state the permissive window produces when the fusion is induced inside it
the 3' partner of the fusion that creates the state
what the permissive combination produces: a CD24-positive pre-leukaemic state