Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries. Due to dynamic clonal changes in a leukemic cell population over time, CLL is characterized by a highly variable clinical course. The expansion of subclones with different gene mutations, many of which are non-recurrent, makes CLL challenging to treat. We aimed to describe the clonal evolution in CLL, focusing on specific treatments and different stages of the disease. As defects in the TP53 gene are strong predictive and prognostic markers in CLL and drive chemoimmunotherapy resistance, we particularly studied factors influencing the clonal development of TP53-mutated subclones.