Analysis of sequential samples: clinical correlations and risk stratification. (A) Scheme of resequencing of mutations in serial samples to determine the time of acquisition and clonal evolution. (B) Kaplan-Meier curves for the probabilities of survival (left panel) and transformation into AML (right panel). Numbers indicate the number of somatic mutations per patient omitting JAK2 V617F and CALR mutations. (C) Time course of the TP53 mutant allele burden in serial follow-up samples of 4 MPN patients with available follow-up samples (upper panel). One patient harbored 2 distinct TP53 mutations (dotted lines), only one of which displayed loss of heterozygosity. Survival (middle panel) and transformation to AML (lower panel) is shown below for 5 patients with mutations in TP53. (D) Time course of the TET2 mutant allele burden in serial follow-up samples of 12 MPN patients (upper panel). Survival (middle panel) and transformation to AML (lower panel) is shown below for 23 patients with mutations in TET2. (E) Time course of the mutant allele burden of epigenetic modifiers (ASXL1, DNMT3A, EZH2, and IDH1) in serial follow-up samples of 11 MPN patients (upper panel). Survival (middle panel) and transformation to AML (lower panel) is shown below for 29 patients with mutations in ASXL1, DNMT3A, EZH2, or IDH1.