Fig. 4: Inflammatory pathways are upregulated in TP53-mutant HSPCs before transformation.
a, Schematic study layout of the CP and paired samples patient cohort selected for TARGET-seq analysis. Created with BioRender.com. b, Clonal evolution of TP53-mutant CP patient samples without clinical evidence of transformation (CP-TP53-MPN, n = 4) and pre-TP53-sAML (patients who subsequently transformed to TP53-sAML) samples (n = 5). The size of the circles is proportional to the average percentage of cells mapping to each clone, and each clone is colored according to its genotype (related to Extended Data Fig. 9e–m). TP53-heterozygous cells selected for subsequent transcriptional analysis are indicated by the blue box. c,d, GSEA of selected differentially expressed pathways (c) and volcano plot of differentially expressed genes (d) in TP53-mutant heterozygous cells from CP TP53-MPN (green; n = 273 cells) and pre-TP53-sAML (orange; n = 296 cells). In d, genes involved in the IFN response are labeled. e, Expression of key IFN-response genes in TP53-heterozygous cells from the same patients as in c and d. In d and e, Padj indicates adjusted P value from combined Fisher’s exact test and Wilcoxon tests, calculated using Fisher’s method and adjusted using Benjamini–Hochberg procedure; FC indicates fold-change. Violin plots indicate log2(counts) distributions and each point represents the expression value of a single cell.
