Shuxin Yao, Rongxia Guo, Wen Tian, Yanbing Zheng, Jin Hu, Guoqiang Han, Rong Yin, Fuling Zhou, Haojian Zhang
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引用次数: 0
摘要
造血干细胞(HSCs)维持着造血生态系统的平衡,而造血生态系统受到多层次的严格调控。急性髓性白血病(AML)是一种严重的血液系统恶性肿瘤,由遗传和表观遗传变化导致白血病干细胞(LSCs)转化。由于 DNA 甲基化相关基因的体细胞突变经常发生在 AML 中,因此 DNA 甲基化被广泛改变,成为启动 AML 的起始引擎。此外,RNA修饰,尤其是N6-甲基腺苷(m6A),在造血生态系统的生成和维持中也发挥着重要作用。鉴于急性髓细胞性白血病发病机制复杂、预后不良,全面了解其发病机制非常重要。在此,我们主要关注造血和急性髓细胞性白血病中的DNA甲基化和RNA m6A修饰,并总结这一领域的最新进展。
Epigenetic modifications in hematopoietic ecosystem: a key tuner from homeostasis to acute myeloid leukemia.
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 N6-methyladenosine (m6A), also play an important role in the generation and maintenance of the hematopoietic ecosystem, and AML development requires reprogramming of m6A 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 m6A modification in hematopoiesis and AML and summarize recent advances in this field.