IMMUNOGENETIC RISK FACTORS FOR ONCOHEMATOLOGICAL DISEASES

HLA (Human Leukocyte Antigens) genes play a key role in regulating the antitumor immune response and are characterized by significant allelic and population polymorphism. Molecules encoded by HLA genes are involved in the selection of the T-cell receptor repertoire, the processing and presentation of neoantigens to T-cells, and the regulation of the cytolytic activity of natural killer cells. The structural features of HLA antigens, and especially the characteristics of the antigen-binding site, determine the effectiveness of their interaction with immunocompetent cells, mediating an individual's susceptibility or resistance to various diseases, including malignancies. Tumor cell evasion of immune control and their unlimited proliferation may result from structural or functional changes in HLA molecules, leading to blockage of neoantigen presentation to cytotoxic T lymphocytes. The causes of such changes may be mutations in the genes encoding the α-chain of HLA class I molecules, the α- and β-chains of HLA class II molecules, as well as in the genes encoding the synthesis of proteins necessary for the proper assembly, transport, expression and functions of HLA molecules (for example, beta-2-microglobulin or the invariant chain of HLA class II molecules). Low or lost expression of HLA molecules on tumor cells also contributes to decreased immune surveillance. Another factor determining the effectiveness of antitumor surveillance is "HLA diversity." Homozygosity of HLA genes narrows the spectrum of neoantigens that can be presented to cytotoxic T cells, weakening antitumor control. This review analyzes HLA genetic factors associated with the risk of developing a number of hematologic malignancies (acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, and diffuse large B-cell lymphoma) in various population groups. HLA markers associated with the response to therapy and long-term prognosis of certain hematologic malignancies are identified. The results of the study of the associations between the HLA phenotype and hematologic malignancies can be used in practice as additional differential diagnostic or prognostic criteria, as well as for the formation of risk groups for developing these diseases.

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