Fig. 3: Clonal evolution of t-MN under platinum treatment in patients without germline TP53 aberrations.

a Phylogenetic tree of clonally expanded HSPCs and bulk t-MN blasts of patient UPN008 (TP53 wild-type). Pie charts indicate the contribution of SBS31 after strict refitting (max_delta < 0.01). The colors of the branches correspond to the type of mutation, clonal, subclonal, or private, which is annotated in the same color text. Small black numbers at splits in the trees indicate in what number of CellPhy bootstraps the split was found, out of 100. b Signature contribution of the mutations in the corresponding branches in the lineage tree on the left. The private HSPC mutations were subsampled to 2000 mutations for visual purposes. 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 IBFM42 (TP53 wild-type). Also single-cell sequenced HSPCs (black squares) and t-MN blasts (black triangles) are included. SBS31 contribution to the clonal branch was supported by 100/100 bootstraps. In the private branch, SBS31 was found in 40/100 bootstraps. d Similar to (b), but for patient IBFM42. e similar to (a), but for patient IBFM32 (TP53 wild-type). f Similar to (b), but for patient IBFM32. g Similar to (a), but for patient IBFM67 (TP53 wild-type). Single-cell t-MN blasts and single HSPCs were sequenced. All sequenced HSPCs shared the KMT2A rearrangement with the t-MN blasts. h Similar to (b), but for patient IBFM67. Source data are provided as a Source Data file.