RUNX1 point mutations potentially identify a subset of early immature T-cell acute lymphoblastic leukaemia that may originate from differentiated T-cells

•RUNX1 is mutated in 6 of 65 T-ALL patients and 5 of 20 T-ALL cell lines.•RUNX1 mutation appears to be associated with early immature T-ALL subtype.•RUNX1-mutated T-ALL cells exhibit TCRγ deletion, a hallmark of mature T-cells.•Early immature T-ALL with RUNX1 mutation may originate from differentiated cells.

The RUNX1/AML1 gene is among the most frequently mutated genes in human leukaemia. However, its association with T-cell acute lymphoblastic leukaemia (T-ALL) remains poorly understood. In order to examine RUNX1 point mutations in T-ALL, we conducted an amplicon-based deep sequencing in 65 Southeast Asian childhood patients and 20 T-ALL cell lines, and detected RUNX1 mutations in 6 patients (9.2%) and 5 cell lines (25%). Interestingly, RUNX1-mutated T-ALL cases seem to constitute a subset of early immature T-ALL that may originate from differentiated T-cells. This result provides a deeper insight into the mechanistic basis for leukaemogenesis.