Foucault Amélie, Hérault Olivier
Department of Biological Hematology, Tours University Hospital, 37000 Tours, France.
INSERM UMR1069 N2COx, Tours University, 37000 Tours, France.
Discov Med. 2024 Dec;36(191):2313-2324. doi: 10.24976/Discov.Med.202436191.213.
Aldehyde dehydrogenases (ALDHs) constitute a group of enzymes that catalyze the oxidation of aldehydes to carboxylic acids. The human ALDH superfamily, including 19 different isoenzymes (ALDH1A1, ALDH1A2, ALDH1A3, AHDH1B1, ALDH1L1, ALDH1L2, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH4A1, ALDH5A1, ALDH6A1, ALDH7A1, ALDH8A1, ALDH9A1, ALDHA16A1, ALDH18A1), displays different key physiological and toxicological functions, with specific tissue expression and substrate specificity. Several studies have established that ALDH are interesting markers for the identification and quantification of human hematopoietic stem cells and cancer stem cells, notably leukemic stem cells. ALDH2 is the best-documented enzyme, in this family, as having an impact on hematology, particularly myeloid malignancies. ALDH2 mainly catalyzes the detoxification of toxic aldehydes (acetaldehyde, formaldehyde). For example, ALDH2 detoxifies formaldehyde, which is produced during the differentiation of hematopoietic progenitors. The trigger of alcohol dehydrogenase 5 (also known as formaldehyde dehydrogenase or S-nitrosoglutathione reductase, ADH5/FDH/GSNOR)/ALDH2 allows to eliminate formaldehyde and ensures normal hematopoiesis. Moreover, the ALDH2*2 variant allele is the most frequent ALDH2 variant, found in 35-45% of individuals of East Asian origin. It is associated with altered acetaldehyde metabolism and is involved in several hematological diseases (aplastic anemia, bone marrow failure, myelodysplastic syndrome). This review presents current knowledge of different members of the ALDH family and their involvement in normal and malignant hematopoiesis. Focus was brought to the ALDH2 isoenzyme in congenital (Fanconi anemia, Aplastic anemia, mental retardation, and dwarfism (AMeD) syndrome, and idiopathic aplastic anemia) and acquired (acute myeloid leukemia and myelodysplastic syndrome) hematological diseases. It also describes the possibilities of using ALDH as both a biomarker and therapeutic target, to identify and eradicate leukemic stem cells in malignant diseases.
醛脱氢酶（ALDHs）是一类催化醛氧化为羧酸的酶。人类ALDH超家族包括19种不同的同工酶（ALDH1A1、ALDH1A2、ALDH1A3、AHDH1B1、ALDH1L1、ALDH1L2、ALDH2、ALDH3A1、ALDH3A2、ALDH3B1、ALDH3B2、ALDH4A1、ALDH5A1、ALDH6A1、ALDH7A1、ALDH8A1、ALDH9A1、ALD16A1、ALDH18A1），具有不同的关键生理和毒理学功能，具有特定的组织表达和底物特异性。多项研究表明，ALDH是鉴定和定量人类造血干细胞及癌症干细胞（尤其是白血病干细胞）的有趣标志物。ALDH2是该家族中记录最充分的对血液学有影响的酶，特别是对髓系恶性肿瘤。ALDH2主要催化有毒醛类（乙醛、甲醛）的解毒。例如，ALDH2可使造血祖细胞分化过程中产生的甲醛解毒。乙醇脱氢酶5（也称为甲醛脱氢酶或S-亚硝基谷胱甘肽还原酶，ADH5/FDH/GSNOR）/ALDH2的触发可消除甲醛并确保正常造血。此外，ALDH2*2变异等位基因是最常见的ALDH2变异，在35%至45%的东亚裔个体中发现。它与乙醛代谢改变有关，并涉及多种血液学疾病（再生障碍性贫血、骨髓衰竭、骨髓增生异常综合征）。本综述介绍了ALDH家族不同成员的现有知识及其在正常和恶性造血中的作用。重点关注了先天性（范可尼贫血、再生障碍性贫血、智力发育迟缓及侏儒症（AMeD）综合征和特发性再生障碍性贫血）和获得性（急性髓系白血病和骨髓增生异常综合征）血液学疾病中的ALDH2同工酶。它还描述了将ALDH用作生物标志物和治疗靶点以识别和根除恶性疾病中白血病干细胞的可能性。
