Fig. 4: Clonal evolution of t-MN under platinum treatment in patients with germline TP53 aberrations.
From: Selective pressures of platinum compounds shape the evolution of therapy-related myeloid neoplasms
a Phylogenetic tree of single HSPCs (black squares) and bulk and single (black triangles) t-MN blasts of patient IBFM22 who had LFS and a TP53-/- t-MN. Pie charts indicate the contribution of SBSD after strict refitting (max_delta < 0.01). Small black numbers at splits in the trees indicate in what number of CellPhy bootstraps the split was found, out of 100. UPD: uniparental disomy b Signature contribution of the mutations in the corresponding branches in the lineage tree on the left. Top: schematic overview of the timeline of the different diagnoses and treatment, including the timing of t-MN development. c Similar to (a), but for patient UPN034 who had LFS. Clonally expanded HSPCs (white squares) were sequenced. Pie charts indicate the contribution of SBS31 after strict refitting (max_delta < 0.01) (d) Similar to (b), but for patient UPN034. The HSPC private mutations were subsampled to 2000 mutations for visual purposes. CH: clonal hematopoiesis, FU: follow-up. In the schematic, the evolution of the t-MN, not the CH, is drawn. 0% blasts were detected in the FU sample by diagnostic MRD measurements. e Similar to (a), but for patient IBFM14 who had a TP53+/- t-MN. Pie charts indicate the contribution of SBS31 after strict refitting (max_delta < 0.01) f Similar to (b), but for patient IBFM14. Source data are provided as a Source Data file.
