SylvainGarciaz Institut Paoli-CalmettesFrance

TP53 mutations are common in AML, often as “multi-hit” types linked to complex karyotypes. Using single-cell DNA sequencing and phenotypic analysis, we examined the zygosity and clonal architecture of TP53m AML. Among eight patients, “multi-hit” TP53 anomalies appeared in blast cells but not in mature lymphoid populations. Minor TP53m heterozygous clones persisted in mature cells and at remission, with dominant “multi-hit” clones resurfacing at relapse. The combined scDNAseq and CITEseq approach highlights distinct mutation patterns, aiding therapy guidance by distinguishing pathological multi-hit mutations from clonal haematopoiesis at remission.