New readers and writers of RNA modifications unique to leukemia stem cells

Chemical modifications of RNA are regulated by a series of readers, writers, and erasers that dictate gene expression. Two new studies in Cell Stem Cell1 Han L. Dong L. Leung K. Zhao Z. Li Y. Gao L. Chen Z. Xue J. Qing Y. Li W. et al. METTL16 drives leukemogenesis and leukemia stem cell self-renewal by reprogramming BCAA metabolism. Cell Stem Cell. . 2022; 30: 52-68 Google Scholar ,2 Cheng Y. Gao Z. Zhang T. Wang Y. Xie X. Han G. Li Y. Yin R. Chen Y. Wang P. et al. Decoding m6A RNA methylome identifies PRMT6-regulated lipid transport promotes AML stem cell maintenance. Cell Stem Cell. . 2022; 30: 69-85 Google Scholar identify roles for the N6-methyladenosine (m6A) methyltransferase METTL16 and the m6A reader IGF2BP2 in leukemia-initiating cells, illuminating exciting new therapeutic targets for leukemia. Chemical modifications of RNA are regulated by a series of readers, writers, and erasers that dictate gene expression. Two new studies in Cell Stem Cell1 Han L. Dong L. Leung K. Zhao Z. Li Y. Gao L. Chen Z. Xue J. Qing Y. Li W. et al. METTL16 drives leukemogenesis and leukemia stem cell self-renewal by reprogramming BCAA metabolism. Cell Stem Cell. . 2022; 30: 52-68 Google Scholar ,2 Cheng Y. Gao Z. Zhang T. Wang Y. Xie X. Han G. Li Y. Yin R. Chen Y. Wang P. et al. Decoding m6A RNA methylome identifies PRMT6-regulated lipid transport promotes AML stem cell maintenance. Cell Stem Cell. . 2022; 30: 69-85 Google Scholar identify roles for the N6-methyladenosine (m6A) methyltransferase METTL16 and the m6A reader IGF2BP2 in leukemia-initiating cells, illuminating exciting new therapeutic targets for leukemia. METTL16 drives leukemogenesis and leukemia stem cell self-renewal by reprogramming BCAA metabolismHan et al.Cell Stem CellJanuary 05, 2023In BriefDeng and colleagues identify METTL16, an m6A writer, as a strong dependency in AML. METTL16 exerts its tumor-promoting role by altering the abundance of m6A-regulated proteins, BCAT1 and BCAT2, and rewiring BCAA metabolism in AML. Full-Text PDF Decoding m6A RNA methylome identifies PRMT6-regulated lipid transport promoting AML stem cell maintenanceCheng et al.Cell Stem CellDecember 26, 2022In BriefCheng et al. delineate a comprehensive m6A landscape during acute myeloid leukemia (AML) development and identify PRMT6, regulated by IGF2BP2, acting as a key for leukemia stem cell maintenance by restraining MFSD2A expression and docosahexaenoic acid levels. These findings provide the rationale for targeting PRMT6-MFSD2A signaling axis in AML therapy. Full-Text PDF