Aberrant Regulation and Targeting of RNA Modifications in Acute Myeloid Leukemia
ZHANG Subo, LI Yuanpei, HUANG Huilin*
AML (acute myeloid leukemia) is a highly heterogeneous hematologic malignancy with a complex pathogenesis involving various epigenetic regulatory mechanisms. In recent years, emerging evidence shows that RNA modifications play a crucial role in the occurrence and development of AML. Particularly, the aberrance of m6A (N6-methyladenosine) in AML has been well and extensively studied. It has been revealed that m6A methylation participates in regulating the maintenance of leukemic stem cell stemness and self-renewal by modulating RNA metabolism in many aspects, including stability, translation efficiency, and splicing. Besides, other RNA modifications, such as ac4C (N4-acetylcytidine), also play key roles in metabolic reprogramming and stemness maintenance of AML cells. This review summarizes the effects of various RNA modifications on gene expression regulation and explores their significant roles in AML. Furthermore, this review compiles the current development and application of small molecule inhibitors targeting RNA modifications and discusses the promising prospects of targeting RNA modifications as a novel therapeutic strategy for AML.
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