РОЛЬ ИЗМЕНЕНИЙ РЕДОКС-СТАТУСА В ПАТОГЕНЕЗЕ ХРОНИЧЕСКОГО ЛИМФОЛЕЙКОЗА

Abstract

Introduction. Chronic lymphocytic leukemia is a hemoblastosis of CD5+ B lymphocytes characterized by lymphocytosis and damages to lymphatic organs and occurring in the older age group. Its etiology and pathogenesis have not been fully understood as of today. Oxidative stress is an important factor in the regulating the hemostasis of hemopoietic stem cells and in activating intracellular survival signaling pathways in chronic lymphocytic leukemia cells. Aim. This study is aimed at analyzing the current data on the role of redox status changes in the pathogenesis of chronic lymphocytic leukemia. Materials and Methods. We reviewed relevant studies published in 2018-2023 and research articles collected in scientific electronic bibliographic databases PubMed and Social Sciences Citation Index, dealing with the pathogenesis of chronic lymphocytic leukemia and the role of free-radical oxidation processes in it. Results and Discussion. In chronic lymphocytic leukemia, oxidative stress with a systemic excess of reactive oxygen species, an imbalance in the effectiveness of antioxidant defense is caused mainly by activation of oxidative phosphorylation in mitochondria, low levels of NADPH-oxidase type 2, increased expression of hemoxygenase-1, glutathione peroxidase and glutathione recycling enzymes, superoxide dismutase-2, thioredoxins, and decreased expression of catalase. Oxidative stress subsequences in the chronic lymphocytic leukemia cells include the activation of transcription factors related to erythroid nuclear factor, nuclear kappa B factor, and FOXO family transcription factors. One of the mechanisms of resistance to drug therapy and oxidative stress of chronic lymphocytic leukemia cells is the intracellular signaling pathway dependent on erythroid nuclear factor-2, due to the activation of expression in cells of superoxide dismutase-2, catalase, glutathione peroxidase, peroxiredoxin-3 and -5, heme oxygenase-1, thioredoxin-1 and -2, reduced glutathione, natural killer cell activity, which is associated with lifespan, chemotaxis, proliferation and survival. FOXO family proteins are believed to suppress carcinogenesis. FOXO3a increases the expression of superoxide dismutase-2, catalase, glutathione peroxidase, peroxiredoxin-3 and -5, and the activity of natural killer cells, which promotes the survival of tumor cells. Conclusion. The development of new targeted pharmacological agents that are capable of accumulating reactive oxygen species and reducing antioxidant protection due to the degradation of erythroid nuclear factor-2 and activation of NADPH-quinone oxidoreductase-1 is underway, which modernizes the therapy of chronic lymphocytic leukemia.