Epigenetic therapies in acute myeloid leukemia: the role of hypomethylating agents, histone deacetylase inhibitors and the combination of hypomethylating agents with histone deacetylase inhibitors  

作　　者：Qing-Yu Xu Li Yu 

机构地区：[1]Department of Hematology-Oncology,International Cancer Center,Shenzhen University General Hospital,Shenzhen University Health Science Center,Shenzhen,Guangdong 518000,China [2]Department of Hematology and Oncology,Medical Faculty Mannheim,Heidelberg University,Mannheim 68169,Germany

出　　处：《Chinese Medical Journal》2020年第6期699-715,共17页中华医学杂志（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(No.81670162,No.81970151,and No.81470010).

摘　　要：Epigenetic regulation includes changes of DNA methylation and modifications of histone proteins and is essential for normal physiologic functions,especially for controlling gene expression.Epigenetic dysregulation plays a key role in disease pathogenesis and progression of some malignancies,including acute myeloid leukemia(AML).Epigenetic therapies,including hypomethylating agents(HMAs)and histone deacetylase(HDAC)inhibitors,were developed to reprogram the epigenetic abnormalities in AML.However,the molecular mechanisms and therapeutic effects of the two agents alone or their combination remain unknown.An overview of these epigenetic therapies is given here.A literature search was conducted through PubMed database,looking for important biological or clinical studies related to the epigenetic regimens in the treatment of AML until October 15th,2019.Various types of articles,including original research and reviews,were assessed,identified,and eventually summarized as a collection of data pertaining the mechanisms and clinical effects of HMAs and HDAC inhibitors in AML patients.We provided here an overview of the current understanding of the mechanisms and clinical therapeutic effects involved in the treatment with HMAs and HDAC inhibitors alone,the combination of epigenetic therapies with intensive chemotherapy,and the combination of both types of epigenetic therapies.Relevant clinical trials were also discussed.Generally speaking,the large number of studies and their varied outcomes demonstrate that effects of epigenetic therapies are heterogeneous,and that HMAs combination regimens probably contribute to significant response rates.However,more research is needed to explore therapeutic effects of HDAC inhibitors and various combinations of HMAs and HDAC inhibitors.

关 键 词：Acute MYELOID leukemia DECITABINE 5-AZACYTIDINE HISTONE DEACETYLASE inhibitors Intensive chemotherapy 

分 类 号：R733.7[医药卫生—肿瘤]