Longitudinal analysis of clonal evolution in CLL patients harboring small TP53 mutated subclones. Graphical illustration of the kinetics of the TP53 mutated populations in 4 representative CLL patients who required treatment at diagnosis and who have been longitudinally investigated by deep-NGS. The x-axis represents time and the y-axis represents allele frequency. TP53 mutations and 17p13 deletion are represented by color-coded circles. The size of the circles is proportional to the allele frequency of the lesion. Arrows indicate the time point at which tumor samples were collected. The relationship between sample collection and treatments is also indicated. BR, bendamustine, rituximab; CLB, chlorambucil; CR, complete response according to the IWCLL-NCI criteria; FCM, fludarabine, cyclophosphamide, mitoxantrone; FCR, fludarabine, cyclophosphamide, rituximab; PD, progressive disease according to the IWCLL-NCI criteria; PR, partial response according to IWCLL-NCI criteria; RDHAP, rituximab, dexamethasone, high-dose cytarabine, cisplatin; Richter, Richter syndrome.