Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA; and.
Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope.
Blood. 2021 Aug 26;138(8):637-648. doi: 10.1182/blood.2019004263.
Protein-coding and noncoding RNAs can be decorated with a wealth of chemical modifications, and such modifications coordinately orchestrate gene expression during normal hematopoietic differentiation and development. Aberrant expression and/or dysfunction of the relevant RNA modification modulators/regulators ("writers," "erasers," and "readers") drive the initiation and progression of hematopoietic malignancies; targeting these dysregulated modulators holds potent therapeutic potential for the treatment of hematopoietic malignancies. In this review, we summarize current progress in the understanding of the biological functions and underlying mechanisms of RNA modifications in normal and malignant hematopoiesis, with a focus on the N6-methyladenosine modification, as well as discuss the therapeutic potential of targeting RNA modifications for the treatment of hematopoietic malignancies, especially acute myeloid leukemia.
蛋白质编码和非编码 RNA 可以被多种化学修饰所修饰,这些修饰协同地在正常造血分化和发育过程中调控基因表达。相关 RNA 修饰调节剂/调控因子(“writers”、“erasers”和“readers”)的异常表达和/或功能障碍驱动了造血恶性肿瘤的发生和进展;针对这些失调的调节剂具有治疗造血恶性肿瘤的强大治疗潜力。在这篇综述中,我们总结了 RNA 修饰在正常和恶性造血中的生物学功能和潜在机制的最新进展,重点介绍了 N6-甲基腺苷修饰,并讨论了针对 RNA 修饰治疗造血恶性肿瘤(尤其是急性髓系白血病)的治疗潜力。