The tRNA Methyltransferase ALKBH8 Promotes Acute Myeloid Leukemia Progression by Regulating Codon-Dependent Gene Expression

Although translation initiation has been extensively studied, the mechanisms governing translation elongation during AML progression remain to be elucidated. Here, we show that the RNA methyltransferase ALKBH8 is overexpressed in AML and is associated with poor prognosis.

ALKBH8 is required for the proliferation and leukemogenic capacity of human and murine AML cells, both in vitro and in vivo. Mechanistically, ALKBH8 promotes translation-coupled mRNA stabilization through its methyltransferase domain. Loss of ALKBH8 induces ribosome pausing and preferentially destabilizes transcripts enriched in adenine-ending codons.