ALKBH1 Drives Tumorigenesis and Drug Resistance via tRNA-decoding Reprogramming and Codon-biased Translation

This study uncovers that ALKBH1-driven tRNA-decoding reprogramming and codon-biased translation, termed "epitranslatomic Midas touch," is crucial for leukemogenesis, leukemia stem cell/leukemia-initiating cell self-renewal, mitochondria structure/function, and resistance to venetoclax. Targeting ALKBH1, especially in combination with venetoclax, offers a promising therapeutic strategy to combat drug resistance in AML and potentially other ALKBH1-overexpressing cancers.