Extended Data Fig. 9: Clonal evolution and molecular signatures of TP53-mutant patients at chronic phase. | Nature Genetics

Extended Data Fig. 9: Clonal evolution and molecular signatures of TP53-mutant patients at chronic phase.

From: Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution

Extended Data Fig. 9

a-b, Flow cytometry profiles of the Lin−CD34+ HSPC compartment in two CP TP53-MPN patients without evidence of clinical transformation (a) and in a representative paired chronic phase (b, up; pre-TP53-sAML) and acute phase (b, bottom; TP53-sAML) sample (Related to Fig. 4a). c-d, Percentage of immunophenotypic HSPC populations in normal donors (n = 8), CP TP53-MPN (n = 4) and pre-TP53-AML patients (n = 5) (c) or in the 5 paired pre-TP53-AML and TP53-AML samples (d). None of the population frequencies are significantly different (p < 0.05) between patient groups by multiple unpaired t-test analysis. In (c), barplot indicates mean ± s.e.m. e-h, Phylogenetic reconstruction of clonal hierarchies in CP TP53-MPN patients from single-cell TARGET-seq genotyping data. In each panel, the phylogenetic tree computed using SCITE is shown on the left, and the number of cells mapping to each clone for each patient, on the right. “pp” indicates posterior probability or each consensus mutation tree, and the probability of each genotype transition is indicated in the square for each mutation. For patient IF9118 (h), baseline (left) and 4 years of follow-up (right) samples are shown separately. i-m, Phylogenetic reconstruction of clonal hierarchies in pre-TP53-AML patients from single-cell TARGET-seq genotyping data (related to Extended Data Fig. 2). In panels (e-m), the size of the circles is proportional to each clone’s size, and is colored according to the genotype indicated in the genotype key. Blue boxes indicate TP53-heterozygous clones used for the analysis presented in Fig. 4c-e. n, Expression of interferon receptors in TP53-heterozygous cells from CP TP53-MPN (n = 273 cells) and pre-TP53-sAML patients (n = 296 cells). “p-adj” 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 (related to Fig. 4d,e). Violin plots indicate log2(counts) distributions and each point represents the expression value of a single-cell. o, GSEA of inflammatory pathways in TP53-mutant heterozygous (n = 284) and homozygous (n = 622) cells from patients GH001 and GR005 at the pre-TP53-sAML stage. NES: Normalized Enrichment Score. FDR: False Discovery Rate.

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