Summary
A bioRxiv preprint describes three recurring leukaemia stem-cell states in paediatric acute myeloid leukaemia and reports that the surface antigens CLEC12A and CD84 together cover them broadly. The findings offer a target-selection framework for future immunotherapy research.
A bioRxiv preprint reports three recurring leukaemia stem-cell states in paediatric acute myeloid leukaemia (AML) and identifies CLEC12A and CD84 as a promising pair of surface-antigen targets across those states. The researchers used single-cell gene-expression and surface-protein measurements to map differences between leukaemia cells, then compared candidate antigens across the resulting cell groups.
The work is a target-discovery analysis, not a report of patients treated with a CLEC12A/CD84 CAR T-cell therapy. Its findings could help guide the design of future immunotherapies intended to recognise a wider range of leukaemia cells.
Three leukaemia stem-cell states
The team combined single-cell transcriptomics with surface-protein profiling using CITE-seq. This approach measures gene activity in individual cells alongside proteins on their surfaces, allowing researchers to compare both the cells’ molecular programmes and the markers that immune therapies might recognise.
The analysis identified three leukaemia stem-cell (LSC) subtypes: primitive (P-LSC), monocytic (M-LSC) and erythroid-like (E-LSC). The authors report that these states often coexist within the same patient, but in different proportions. Each had a characteristic transcriptional programme and surface-protein profile.
That variation matters for immune targeting. A treatment aimed at one surface antigen may recognise cells carrying that marker while missing other leukaemia cell states with a different profile. The study therefore assessed antigen coverage across the three groups rather than treating the leukaemia as a uniform population.
Why the study pairs CLEC12A with CD84
In the researchers’ analysis, CLEC12A was present across P-LSC and M-LSC cells but was largely absent from E-LSC cells. CD84 offered complementary coverage in the primitive and monocytic groups and was the main target identified in the erythroid-like group. The authors report that combining the two antigens provided broad coverage across all three LSC subtypes while sparing healthy haematopoietic stem cells.
The team also reports validation of the combination in independent single-cell and bulk datasets. Together, the results provide a paediatric-specific framework for prioritising antigens and a rationale for exploring dual-target CAR T-cell designs. CAR T cells are engineered immune cells given receptors that help them recognise selected targets; choosing targets shared by more cancer-cell states could be important where those states coexist.
The report is a preprint. Its abstract does not give cohort sizes or numerical antigen-coverage estimates, and it describes target profiling rather than a test of treatment effectiveness in patients. The findings therefore support further evaluation of the target pair, rather than demonstrating clinical benefit.