METTL16 drives leukemogenesis and leukemia stem cell self-renewal by reprogramming BCAA metabolism.

ABSTRACT: N⁶-methyladenosine (m⁶A), the most prevalent internal modification in mammalian mRNAs, is involved in many pathological processes. METTL16 is a recently identified m⁶A 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,

SUBMITTER: Han L 

PROVIDER: S-EPMC9838187 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature