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造血生态系统中的表观遗传修饰:从稳态到急性髓系白血病的关键调节因素

Epigenetic modifications in hematopoietic ecosystem: a key tuner from homeostasis to acute myeloid leukemia.

作者信息

Yao Shuxin, Guo Rongxia, Tian Wen, Zheng Yanbing, Hu Jin, Han Guoqiang, Yin Rong, Zhou Fuling, Zhang Haojian

机构信息

State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.

Department of Hematology, Zhongnan Hospital, Medical Research Institute, Wuhan University, Wuhan, China.

出版信息

Blood Sci. 2024 Sep 12;6(4):e00206. doi: 10.1097/BS9.0000000000000206. eCollection 2024 Oct.

Abstract

Hematopoietic stem cells (HSCs) maintain homeostasis in the hematopoietic ecosystem, which is tightly regulated at multiple layers. Acute myeloid leukemia (AML) is a severe hematologic malignancy driven by genetic and epigenetic changes that lead to the transformation of leukemia stem cells (LSCs). Since somatic mutations in DNA methylation-related genes frequently occur in AML, DNA methylation is widely altered and functions as a starting engine for initiating AML. Additionally, RNA modifications, especially N-methyladenosine (mA), also play an important role in the generation and maintenance of the hematopoietic ecosystem, and AML development requires reprogramming of mA modifications to facilitate cells with hallmarks of cancer. Given the complex pathogenesis and poor prognosis of AML, it is important to fully understand its pathogenesis. Here, we mainly focus on DNA methylation and RNA mA modification in hematopoiesis and AML and summarize recent advances in this field.

摘要

造血干细胞(HSCs)维持造血生态系统的稳态,该系统在多个层面受到严格调控。急性髓系白血病(AML)是一种严重的血液系统恶性肿瘤,由导致白血病干细胞(LSCs)转化的遗传和表观遗传变化驱动。由于DNA甲基化相关基因的体细胞突变在AML中频繁发生,DNA甲基化广泛改变,并作为引发AML的启动引擎发挥作用。此外,RNA修饰,尤其是N6-甲基腺苷(m6A),在造血生态系统的产生和维持中也起着重要作用,而AML的发展需要重新编程m6A修饰以促进具有癌症特征的细胞。鉴于AML复杂的发病机制和不良预后,全面了解其发病机制非常重要。在此,我们主要关注造血和AML中的DNA甲基化和RNA m6A修饰,并总结该领域的最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23a9/11398801/700fb610bb6b/bs9-6-e00206-g001.jpg

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