Clonal evolution in chronic lymphocytic leukemia is associated with an unmutated IGHV status and frequently leads to a combination of loss of TP53 and TP53 mutation

Background Chromosomal abnormalities and gene mutations determine the prognosis of patients with chronic lymphocytic leukemia (CLL). Genetic lesions can be acquired by clonal evolution (CE) likely correlating with clinical progression. Methods and Results Samples of 169 CLL patients were analyzed for cytogenetic clonal evolution (CCE) and CE affecting the genes TP53 and SF3B1 . Moreover, the mutational status of IGHV and the clinical outcome was evaluated. CCE was observed in 35% of CLL patients. The most frequently gained cytogenetic aberration was a deletion of TP53 . Acquired TP53 deletion was more frequent in patients with SF3B1 mutations compared to those without (19% vs. 7%). CCE showed a tendency to occur more frequently in patients with an aberrant karyotype at first investigation than in patients with a normal karyotype. In 73% of patients with CCE (p = 0.002) and 92% of patients with CE affecting the genes TP53 and SF3B1 (p