Figure 4.

Clonal evolution analysis of each of the 5 patients during idasanutlin therapy. Fish plots show the selected models for clonal evolution history of 5 patients during idasanutlin therapy. The width of clones in each time point represents the estimated CCFs of each subclone population. For patient 1 (A-B), patient 2 (C-D), and patient 4 (F-G), two models are shown. The first model presents a scenario in which TP53 mutations are a minor subclone of JAK2V617F (A,C,F), and the second model represents a scenario in which the TP53 mutant and JAK2V617F exist in 2 independent subclones. Patient 3 (E) is the only patient whose data imply the existence of 2 independent TP53- and JAK2V617–mutated subclones. Patient 5 (H) is the only patient in whom mutated TP53 is unequivocally a subclone of the JAK2V617F founder clone. It must be noted that due to the relatively small number of somatic mutations in each sample, there are multiple models per patient, and the models presented are selected solely based on the relationship of TP53 and JAK2 mutations.