Osikov M V, Korobkin E A, Fedosov A A, Sineglazova A V
South Ural State Medical University, Ministry of Health of the Russian Federation, Chelyabinsk, Russia.
Chelyabinsk Regional Clinical Hospital, Chelyabinsk, Russia.
Dokl Biochem Biophys. 2024 Dec;519(1):564-570. doi: 10.1134/S1607672924701217. Epub 2024 Oct 31.
Chronic lymphocytic leukemia is a hemoblastosis of CD5 B lymphocytes with lymphocytosis, damage to the lymphatic organs, occurring in the older age group, the etiology and pathogenesis of which are not fully understood. Oxidative stress is an important factor in the regulation of stem cells and the activation of intracellular survival signaling pathways in chronic lymphocytic leukemia cells. The aim of the study was to analyze the current data on the role of redox status changes in the pathogenesis of chronic lymphocytic leukemia. A review of published relevant studies 2018-2023, scientific articles in scientific electronic bibliographic databases PubMed and Social Sciences Citation Index, devoted to the pathogenesis of chronic lymphocytic leukemia and the role of free-radical oxidation processes in it was carried out. 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 heme oxygenase-1, glutathione peroxidase and glutathione recycling enzymes, superoxide dismutase-2, thioredoxins and decreased expression of catalase. 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. 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.
慢性淋巴细胞白血病是一种CD5 B淋巴细胞的造血系统疾病，伴有淋巴细胞增多，损害淋巴器官，发病于老年人群体，其病因和发病机制尚未完全明确。氧化应激是慢性淋巴细胞白血病细胞中干细胞调节及细胞内生存信号通路激活的一个重要因素。本研究旨在分析当前关于氧化还原状态变化在慢性淋巴细胞白血病发病机制中作用的数据。对2018 - 2023年已发表的相关研究进行了综述，这些研究来自科学电子文献数据库PubMed和社会科学引文索引中的科学文章，致力于慢性淋巴细胞白血病的发病机制以及其中自由基氧化过程的作用。在慢性淋巴细胞白血病中，氧化应激伴随着全身活性氧的过量、抗氧化防御有效性的失衡，主要是由线粒体氧化磷酸化的激活、2型NADPH氧化酶水平降低、血红素加氧酶 - 1、谷胱甘肽过氧化物酶和谷胱甘肽循环酶、超氧化物歧化酶 - 2、硫氧还蛋白的表达增加以及过氧化氢酶的表达降低所引起的。慢性淋巴细胞白血病细胞对药物治疗和氧化应激的耐药机制之一是依赖于红系核因子 - 2的细胞内信号通路，这是由于超氧化物歧化酶 - 2、过氧化氢酶、谷胱甘肽过氧化物酶、过氧化物还原酶 - 3和 - 5、血红素加氧酶 - 1、硫氧还蛋白 - 1和 - 2、还原型谷胱甘肽、自然杀伤细胞活性在细胞中的表达激活所致，这与细胞寿命、趋化性、增殖和存活相关。FOXO家族蛋白被认为可抑制致癌作用。FOXO3a增加超氧化物歧化酶 - 2、过氧化氢酶、谷胱甘肽过氧化物酶、过氧化物还原酶 - 3和 - 5的表达以及自然杀伤细胞的活性，这促进了肿瘤细胞的存活。目前正在开发新的靶向药理剂，这些药物能够积累活性氧并由于红系核因子 - 2的降解和NADPH - 醌氧化还原酶 - 1的激活而降低抗氧化保护，这使慢性淋巴细胞白血病的治疗更加现代化。
