Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Ann Med. 2022 Dec;54(1):2011-2023. doi: 10.1080/07853890.2022.2099578.
DNA methylation is considered an essential epigenetic event during leukaemogenesis and the emergence of drug resistance, which is primarily regulated by DNA methyltransferases. DNA methyltransferase-1 (DNMT1) is one of the members of DNA methyltransferases, in charge of maintaining established methylation. Recently, DNMT1 is shown to promote malignant events of cancers through the epigenetic and non-epigenetic processes. Increasing studies in solid tumours have identified DNMT1 as a therapeutic target and a regulator of therapy resistance; however, it is unclear whether DNMT1 is a critical regulator in acute myeloid leukaemia (AML) and how it works. In this review, we summarized the recent understanding of DNMT1 in normal haematopoiesis and AML and discussed the possible functions of DNMT1 in promoting the development of AML and predicting the sensitivity of hypomethylation agents to better understand the relationship between DNMT1 and AML and to look for new hope to treat AML patients.Key messagesThe function of DNA methyltransferase-1 in acute myeloid leukaemia.DNA methyltransferase-1 predicts the sensitivity of drug and involves the emergence of drug resistance.
DNA 甲基化被认为是白血病发生和耐药性出现过程中的一个重要表观遗传事件，主要由 DNA 甲基转移酶（DNA methyltransferase，DNMT）调控。DNMT1 是 DNA 甲基转移酶家族的成员之一，负责维持已建立的甲基化。最近，DNMT1 通过表观遗传和非表观遗传过程促进癌症的恶性事件。越来越多的实体瘤研究将 DNMT1 确定为治疗靶点和治疗耐药性的调节剂；然而，尚不清楚 DNMT1 在急性髓系白血病（AML）中是否是关键调控因子，以及其具体作用机制。在本综述中，我们总结了 DNMT1 在正常造血和 AML 中的最新认识，并讨论了 DNMT1 促进 AML 发展和预测低甲基化药物敏感性的可能作用，以更好地理解 DNMT1 与 AML 之间的关系，并寻找新的希望来治疗 AML 患者。
关键信息
DNA 甲基转移酶 1 在急性髓系白血病中的作用。
DNA 甲基转移酶 1 预测药物敏感性并涉及耐药性的出现。
