期刊
CELL STEM CELL
卷 22, 期 2, 页码 191-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2017.11.016
关键词
-
资金
- NIH R01 Grants [CA214965, CA211614, CA178454, CA182528, R50 CA211404, RM1 HG008935]
- National Nature Science Foundation of China [81673475, 81373427, 91440110]
- Academic and Research Committee of Cincinnati Children's Hospital Medical Center
N-6-methyladenosine (m(6)A), the most prevalent internal modification in eukaryotic messenger RNAs (mRNAs), plays critical roles in many bioprocesses. However, its functions in normal and malignant hematopoiesis remain elusive. Here, we report that METTL14, a key component of the m(6)A methyltransferase complex, is highly expressed in normal hematopoietic stem/progenitor cells (HSPCs) and acute myeloid leukemia (AML) cells carrying t(11q23), t(15; 17), or t(8; 21) and is downregulated during myeloid differentiation. Silencing of METTL14 promotes terminal myeloid differentiation of normal HSPCs and AML cells and inhibits AML cell survival/proliferation. METTL14 is required for development and maintenance of AML and self-renewal of leukemia stem/initiation cells (LSCs/LICs). Mechanistically, METTL14 exerts its oncogenic role by regulating its mRNA targets (e.g., MYB and MYC) through m(6)A modification, while the protein itself is negatively regulated by SPI1. Collectively, our results reveal the SPI1-METTL14-MYB/MYC signaling axis in myelopoiesis and leukemogenesis and highlight the critical roles of METTL14 and m(6)A modification in normal and malignant hematopoiesis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据