The Role of RNA Methyltransferase METTL3 in Normal and Malignant Hematopoiesis

m(6)A modification is the most common modification in eukaryotes. METTL3, as a core methyltransferase of m(6)A modification, plays a vital role in normal and malignant hematopoiesis. Recent studies have shown that METTL3 is required for normal and symmetric differentiation of hematopoietic stem/progenitor cells (HSPCs). Moreover, METTL3 strongly impacts the process and development of hematological neoplasms, including the differentiation, apoptosis, proliferation, chemoresistance, and risk of tumors. Novel inhibitors of METTL3 have been identified and studied in acute myeloid leukemia (AML) cells. STM2457, a selective inhibitor of METTL3, has been identified to block proliferation and promote differentiation and apoptosis of AML cells without impacting normal hematopoiesis. Therefore, in our present review, we focus on the structure of METTL3, the role of METTL3 in both normal and malignant hematopoiesis, and the potential of METTL3 for treating hematological neoplasms.

Automated summary

METTL3 is a core methyltransferase involved in m(6)A modification and plays a vital role in normal and malignant hematopoiesis. It affects the differentiation, apoptosis, proliferation, chemoresistance, and risk of tumors in hematological neoplasms. Inhibitors of METTL3, such as STM2457, have shown potential in treating acute myeloid leukemia by blocking proliferation and promoting differentiation and apoptosis of cancer cells.