DNA methylation in normal and malignant hematopoiesis
DNA methylation in normal and malignant hematopoiesis
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DOI：
10.1007/s12185-016-1957-7
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发表时间：
2016-06-01
影响因子：
2.1
通讯作者：
Challen, Grant A.
中科院分区：
文献类型：
--
作者：
Celik, Hamza;Kramer, Ashley;Challen, Grant A.
DNA甲基化的研究自20世纪60年代以来一直是一个快速发展的领域。DNA甲基化是一种表观遗传修饰，在引导干细胞向其指定谱系分化和维持组织稳态方面起着至关重要的作用。此外，异常DNA甲基化已被充分表征为多种癌症发病机制中的重要贡献因素。造血是一个过程，是唯一容易受到表观遗传变化，由于活跃的循环干细胞的小池，产生整个成熟的免疫造血系统。DNA甲基转移酶的突变已被证明是血液恶性肿瘤（如急性髓性白血病）发展的起始事件，因此已成为改进诊断和治疗的目标。DNA甲基化在造血发育层次中的时空调控对造血稳态至关重要。进一步了解DNA甲基化在正常和恶性造血中的作用将对再生干细胞治疗和造血恶性肿瘤的临床治疗产生重大影响。本次审查旨在突出该领域的当前发展，并优先考虑未来的研究方向。
The study of DNA methylation has been a rapidly expanding field since its dawn in the 1960s. DNA methylation is an epigenetic modification that plays a crucial role in guiding the differentiation of stem cells to their destined lineage, and in maintaining tissue homeostasis. Moreover, aberrant DNA methylation has been well characterized as a significant contributing factor in the pathogenesis of a variety of cancers. Hematopoiesis is a process that is uniquely susceptible to epigenetic changes due to the small pool of actively cycling stem cells that give rise to the entire mature immune-hematopoietic system. Mutations in DNA methyltransferase enzymes have been shown to be initiating events in the development of hematological malignancies such as acute myeloid leukemia and, therefore, have become targets for improved diagnostics and therapy. The spatial and temporal regulation of DNA methylation in the hematopoietic developmental hierarchy is critical to hematopoietic homeostasis. An improved understanding of the roles that DNA methylation plays in normal and malignant hematopoiesis will have a significant impact on the future of regenerative stem cell therapy and clinical treatment of hematopoietic malignancies. This review aims to highlight current developments in the field and prioritize future research directions.