Zhang Juan, Gao Xuefeng, Yu Li
Department of Hematology and Oncology, International Cancer Center, Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University Health Science Center, Shenzhen, China.
Front Oncol. 2021 Sep 1;11:741746. doi: 10.3389/fonc.2021.741746. eCollection 2021.
Accurate orchestration of gene expression is critical for the process of normal hematopoiesis, and dysregulation is closely associated with leukemogenesis. Epigenetic aberration is one of the major causes contributing to acute myeloid leukemia (AML), where chromosomal rearrangements are frequently found. Increasing evidences have shown the pivotal roles of histone deacetylases (HDACs) in chromatin remodeling, which are involved in stemness maintenance, cell fate determination, proliferation and differentiation, mastering the transcriptional switch of key genes. In abnormal, these functions can be bloomed to elicit carcinogenesis. Presently, HDAC family members are appealing targets for drug exploration, many of which have been deployed to the AML treatment. As the majority of AML events are associated with chromosomal translocation resulting in oncogenic fusion proteins, it is valuable to comprehensively understand the mutual interactions between HDACs and oncogenic proteins. Therefore, we reviewed the process of leukemogenesis and roles of HDAC members acting in this progress, providing an insight for the target anchoring, investigation of hyperacetylated-agents, and how the current knowledge could be applied in AML treatment.
基因表达的精确调控对于正常造血过程至关重要，而失调则与白血病发生密切相关。表观遗传异常是导致急性髓系白血病（AML）的主要原因之一，在AML中经常发现染色体重排。越来越多的证据表明组蛋白去乙酰化酶（HDACs）在染色质重塑中起关键作用，其参与干性维持、细胞命运决定、增殖和分化，掌控关键基因的转录开关。异常情况下，这些功能会被放大从而引发致癌作用。目前，HDAC家族成员是药物研发的有吸引力的靶点，其中许多已被用于AML治疗。由于大多数AML事件与导致致癌融合蛋白的染色体易位有关，全面了解HDACs与致癌蛋白之间的相互作用具有重要价值。因此，我们综述了白血病发生过程以及HDAC成员在此过程中的作用，为靶点定位、高乙酰化剂的研究以及当前知识如何应用于AML治疗提供见解。
