Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Department of Haematology and.
Blood. 2022 Apr 7;139(14):2119-2129. doi: 10.1182/blood.2019004316.
Reactive aldehydes are potent genotoxins that threaten the integrity of hematopoietic stem cells and blood production. To protect against aldehydes, mammals have evolved a family of enzymes to detoxify aldehydes, and the Fanconi anemia DNA repair pathway to process aldehyde-induced DNA damage. Loss of either protection mechanisms in humans results in defective hematopoiesis and predisposition to leukemia. This review will focus on the impact of genotoxic aldehydes on hematopoiesis, the sources of endogenous aldehydes, and potential novel protective pathways.
反应性醛类是强有力的遗传毒素，会威胁到造血干细胞和血液生成的完整性。为了防止醛类的侵害，哺乳动物进化出了一组酶来解毒醛类，还进化出了范可尼贫血症 DNA 修复途径来处理醛类引起的 DNA 损伤。人类如果失去这两种保护机制中的任何一种，都会导致造血功能缺陷和易患白血病。这篇综述将重点讨论遗传毒性醛类对造血的影响、内源性醛类的来源，以及潜在的新的保护途径。
