State Key Laboratory of Common Mechanism Research for Major Diseases, State Key Laboratory for Complex, Severe, and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences / Peking Union Medical College, Beijing 100005, China.
Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Chin Med J (Engl). 2024 May 5;137(9):1033-1043. doi: 10.1097/CM9.0000000000003073. Epub 2024 Mar 28.
Epitranscriptomics focuses on the RNA-modification-mediated post-transcriptional regulation of gene expression. The past decade has witnessed tremendous progress in our understanding of the landscapes and biological functions of RNA modifications, as prompted by the emergence of potent analytical approaches. The hematopoietic system provides a lifelong supply of blood cells, and gene expression is tightly controlled during the differentiation of hematopoietic stem cells (HSCs). The dysregulation of gene expression during hematopoiesis may lead to severe disorders, including acute myeloid leukemia (AML). Emerging evidence supports the involvement of the mRNA modification system in normal hematopoiesis and AML pathogenesis, which has led to the development of small-molecule inhibitors that target N6-methyladenosine (m 6 A) modification machinery as treatments. Here, we summarize the latest findings and our most up-to-date information on the roles of m 6 A and N7-methylguanine in both physiological and pathological conditions in the hematopoietic system. Furthermore, we will discuss the therapeutic potential and limitations of cancer treatments targeting m 6 A.
表观转录组学专注于 RNA 修饰介导的基因表达的转录后调控。过去十年,由于强大的分析方法的出现,我们对 RNA 修饰的图谱和生物学功能的理解取得了巨大的进展。造血系统为血细胞提供了终生的供应,并且在造血干细胞 (HSCs) 的分化过程中,基因表达受到严格控制。造血过程中基因表达的失调可能导致严重的疾病,包括急性髓系白血病 (AML)。新出现的证据支持 mRNA 修饰系统参与正常造血和 AML 发病机制,这导致了针对 N6-甲基腺苷 (m6A) 修饰机制的小分子抑制剂作为治疗方法的开发。在这里,我们总结了 m6A 和 N7-甲基鸟嘌呤在造血系统生理和病理条件下的最新发现和我们的最新信息。此外,我们将讨论针对 m6A 的癌症治疗的治疗潜力和局限性。