Factors associated with presence of unfavorable ТР53 and SF3B1 mutations in chronic lymphocytic leukemia patients

Summary. The aim of the study was to identify factors, associated with the presence of unfavorable ТР53 and SF3B1 mutations in chronic lymphocytic leukemia (CLL) patients. ТР53 mutations were studied in 261 CLL patients (together with the study of SF3B1 mutations in 244 patients) by direct sequencing and with evaluation of some ­others risk factors (baseline characteristics of patients, mutational status of immunoglobulin heavy chain variable region (IGHV) genes, polymorphisms of CD38 gene, genes of apoptosis regulation and DNA repair system). Only mutational status of IGHV genes and rs1042522 ТР53 were associated with an increased incidence of TP53 and SF3B1 mutations. In carriers of Arg/Arg and Arg/Pro genotypes risk of incidence of TP53 and SF3B1 was increased in UM compared with M IGHV genes (OR 1,182; 95% CI 1,083–1,290; р=0,003). In carriers of Arg/Arg and Arg/Pro genotypes and expression of М IGHV genes risk of incidence of TP53 and SF3B1 was increased under expression of IGHV4-59, IGHV3-30 and IGHV3-21 genes compared with patients expressed others M IGHV genes (OR=1,430; 95% CI 1,026–1,993; р=0,001). The Pro/Pro genotype was associated with an increased incidence of TP53 and SF3B1 mutations regardless of mutational status and expression of separate IGHV genes. The study of mutational status, expression of separate IGHV genes and rs1042522 ТР53 polymorphism may be used as a risk factor for incidence of TP53 and SF3B1 mutations in CLL patients.