| First Author | Han L | Year | 2023 |
| Journal | Cell Stem Cell | Volume | 30 |
| Issue | 1 | Pages | 52-68.e13 |
| PubMed ID | 36608679 | Mgi Jnum | J:355226 |
| Mgi Id | MGI:7427294 | Doi | 10.1016/j.stem.2022.12.006 |
| Citation | Han L, et al. (2023) METTL16 drives leukemogenesis and leukemia stem cell self-renewal by reprogramming BCAA metabolism. Cell Stem Cell 30(1):52-68.e13 |
| abstractText | N(6)-methyladenosine (m(6)A), the most prevalent internal modification in mammalian mRNAs, is involved in many pathological processes. METTL16 is a recently identified m(6)A methyltransferase. However, its role in leukemia has yet to be investigated. Here, we show that METTL16 is a highly essential gene for the survival of acute myeloid leukemia (AML) cells via CRISPR-Cas9 screening and experimental validation. METTL16 is aberrantly overexpressed in human AML cells, especially in leukemia stem cells (LSCs) and leukemia-initiating cells (LICs). Genetic depletion of METTL16 dramatically suppresses AML initiation/development and maintenance and significantly attenuates LSC/LIC self-renewal, while moderately influencing normal hematopoiesis in mice. Mechanistically, METTL16 exerts its oncogenic role by promoting expression of branched-chain amino acid (BCAA) transaminase 1 (BCAT1) and BCAT2 in an m(6)A-dependent manner and reprogramming BCAA metabolism in AML. Collectively, our results characterize the METTL16/m(6)A/BCAT1-2/BCAA axis in leukemogenesis and highlight the essential role of METTL16-mediated m(6)A epitranscriptome and BCAA metabolism reprograming in leukemogenesis and LSC/LIC maintenance. |
