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Chronic lymphocytic leukemia (CLL) is one of the most common B-cell malignancies in Western countries. IGHV mutational status is the most important prognostic factor for this disease. CLL is characterized by an extreme narrowing of the IGHV genes repertoire and the existence of subgroups of quasi-identical stereotyped antigenic receptors (SAR). Some of these subgroups have already been identified as independent prognostic factors for CLL. Here, we report the frequencies of TP53, NOTCH1, and SF3B1 gene mutations and chromosomal aberrations assessed by NGS and FISH in 152 CLL patients with the most common SAR in Russia. We noted these lesions to be much more common in patients with certain SAR than average in CLL. The profile of these aberrations differs between the subgroups of SAR, despite the similarity of their structure. For most of these subgroups mutations prevailed in a single gene, except for CLL#5 with all three genes affected by mutations. It should be noted that our data concerning the mutation frequency in some SAR groups differ from that obtained previously, which could be due to the population differences between patient cohorts. The research in this area should be important for better understanding the pathogenesis of CLL and therapy optimization.

Introduction. An unfavorable prognosis in chronic lymphocytic leukemia (CLL) is associated with unmutated status of rearranged IGHV genes. CLL is also characterized by a narrowing of the repertoire of IGHV genes and the formation of quasiidentical (stereotyped) receptors, which is probably associated with antigenic selection of the tumor B-cell clone in the pathogenesis of the disease. The HLA phenotype plays an important role in antigenic selection of B cells. On the other hand, the association of specifi c HLA alleles with various diseases has been described. Aim. To assess the frequencies of HLA alleles in CLL patients with unmutated IGHV genes and the most common stereotyped receptors (SARs). Materials and methods. The study included 100 CLL patients with unmutated IGHV genes - 50 with the most common stereotyped antigen receptors (SARs) and 50 with non-stereotyped antigenic receptors. Control group of healthy donors was also included. Results. Signifi cant differences in HLA-allele repertoire between this two groups of patients and groups of donors were found. B*18 allele group was found much more common in patients with SARs than in donors and in patients without SARs. HLA-B*39 was more frequent for patients with SARs compared to donors; in patients without SARs these alleles were not found. For all patients, the frequency of HLA-B*52 alleles was higher than for donors. HLA-C*12 allelic group was found more frequent in CLL patients than in donors. HLA-DRB1*15 in CLL patients with SARs was found twice as often as in healthy donors or patients without SARs, while HLA-DRB1*13, oppositely, was found twice as rare. HLA-DRB1*16 was signifi cantly more frequent in patients without SARs, compared with donors and the patients with SARs. No signifi cant differences were found in the HLA-A and HLA-DQB1 loci. Conclusion. The association of two HLA alleles with “unmutated” CLL and two others with CLL bearing prognostically unfavorable SARs was found. HLA typing of expanded samples of CLL patients with different prognosis and course of the disease will provide more information on the mechanisms of antigen selection in the pathogenesis of CLL and improve diagnostic and therapeutic approaches.

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