AUTHOR=Wu Xia , Ye Wu , Gong Yuping 

TITLE=The Role of RNA Methyltransferase METTL3 in Normal and Malignant Hematopoiesis

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.873903

DOI=10.3389/fonc.2022.873903

ISSN=2234-943X

ABSTRACT=<p>m<sup>6</sup>A modification is the most common modification in eukaryotes. <italic>METTL3</italic>, as a core methyltransferase of m<sup>6</sup>A modification, plays a vital role in normal and malignant hematopoiesis. Recent studies have shown that <italic>METTL3</italic> is required for normal and symmetric differentiation of hematopoietic stem/progenitor cells (HSPCs). Moreover, <italic>METTL3</italic> strongly impacts the process and development of hematological neoplasms, including the differentiation, apoptosis, proliferation, chemoresistance, and risk of tumors. Novel inhibitors of <italic>METTL3</italic> have been identified and studied in acute myeloid leukemia (AML) cells. STM2457, a selective inhibitor of <italic>METTL3</italic>, 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 <italic>METTL3</italic>, the role of <italic>METTL3</italic> in both normal and malignant hematopoiesis, and the potential of <italic>METTL3</italic> for treating hematological neoplasms.</p>