Fig. 3: The development of treatment-related AMLs.

a Relative activity of platinum-related signature among clonal mutations (with respect to subclonal mutations) across tAMLs and the metastatic tumors of several organs of origin. The box in each boxplot delimits the first and third quartiles of the distribution (with a line representing the median); the whiskers delimit the lowest data point above the first quartile minus 1.5 times the interquartile distance and the highest data point below the third quartile plus 1.5 times the interquartile distance. b Mutational profile of the HSC signature active across tAML cases. c Linear relationship between the age of patients and the number of HSC mutations of primary AMLs (blue dots). The gray dots correspond to healthy blood donors and thus the regression of their HSC mutation burden to the age represents the normal accumulation of mutations in the process of hematopoiesis. In the figure r represents the two-tailed Pearson’s correlation coefficient and p, its associated p-value. The shaded areas cover the 95% confidence intervals of the corresponding regression lines. d A non-significant regression is obtained between the HSC mutation burden and the age of patients with tAML. In the figure r represents the Pearson’s correlation coefficient and p, its associated p-value. The shaded area covers the 95% confidence intervals of the regression line. e Genes with detectable signals of positive selection across the subset of 261 AMLs of the WES AML cohort with a healthy control sample. The recurrence of mutation shown by the bars is measured across the entire cohort. f Overrepresentation of mutations of different genes across primary or treatment-related AMLs. Significant cases (Benjamini-Hochberg FDR < 0.05) appear circled. The bars represent the 95% confidence intervals of the log-odds ratio. SBS single base substitution, HSC hematopoietic stem cell, sig signature.