Clonal selection and expansion of TP53-mutated subclones during the clinical course of CLL. Yellow circles indicate the TP53-mutated CLL cell which expands through the disease course from below the level of conventional detection methods at diagnosis to become the dominant population in refractory disease. Blue circles indicate the non-TP53–mutated CLL cell which is the dominant clone at diagnosis but is subsequently replaced by the TP53-mutated subclone.