Association of the frequency of sf3b1 gene mutations in chronic lymphocytic leukemia patients with the structure of the b-cell receptor

Introduction. The course of chronic lymphocytic leukemia (CLL) varied from indolent to rapidly progressive. Stratification of CLL patients into risk groups is based on the stage of disease, the mutational status of immunoglobulin variable region genes (IGHV genes), and mutations of ТР53, NOTCH1, and SF3B1 genes. The frequency of SF3B1 gene mutations increases significantly in the progression of CLL. Aim: to determine the group of CLL patients with increased risk of developing SF3B1 mutations. Material and methods. Analysis was performed on the group of 261 CLL patients. The SF3B1 mutations and IGHV gene mutational status were studied by polymerase chain reaction (PCR) followed by direct sequencing. Results. SF3B1 mutations were identified in 30 patients (11.5%). The frequency of mutations did not differ among primary patients (8.6%) and patients examined before the start of the first line of therapy (9.9%) but increased in relapsed patients (23.8%), p = 0,01. In cases with the expression of IGHV3-21, IGHV3-30, IGHV4-59, and IGHV4-61 genes, regardless of their mutational status, the risk of developing SF3B1 mutations increased 4.97 times (95% CI = 2.21–11.19; p = 0.000047). In addition, stereotypy of the B-cell receptor (cluster #2), the risk of SF3B1 gene mutations increased in 8.65 times (95% CI = 1.66–45.05; p = 0.0027). Conclusion. The expression of individual IGHV genes and the configuration of the B-cell receptor are significant measure the probability of occurrence of SF3B1 gene mutations. Key words: chronic lymphocytic leukemia, SF3B1 gene mutations, IGHV genes, B-cell receptor stereotype