Fig. 1: Clonal evolution of TP53-sAML.

a, Schematic study layout for TARGET-seq profiling of 17517 Lin^-CD34⁺ HSPCs from 31 donors. b–e, Representative examples of the four major patterns of clonal evolution in TP53-sAML patients: bi-allelic mutations (b), hemizygous mutations (c), parallel evolution (d) and JAK2 negative bi-allelic evolution (e). The numbers in parenthesis indicate the number of patients in each category. The size of the circles is proportional to each clone’s size, indicated as a percentage of total Lin^-CD34⁺ cells for one representative patient in each group; each clone is colored according to its genotype (related to Extended Data Fig. 2b–o) and red boxes indicate TP53 multihit clones. f, Representative examples from integrated mutation and CNA-based clonal hierarchies. Solid lines indicate the acquisition of a genetic hit (that is point mutation or CNA), whereas dotted lines indicate the specific genetic hit acquired in each step of the hierarchy (related to Extended Data Fig. 2p,q). g, Proportion of TP53 multihit cells classified as carrying clonal or subclonal CNAs in each patient, using a transcriptomic-based CNA clustering approach (inferCNV). h, Experimental strategy for xenotransplantation of CD34⁺ cells from TP53-sAML patients in immunodeficient mice. i, Percentage of cells carrying CNAs found in each PDX and corresponding Lin^-CD34⁺ cells from the primary TP53-sAML sample transplanted (related to Extended Data Fig. 3; n = 1). j, Model of TP53-sAML genetic evolution. Created with BioRender.com.