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Updated: Oct 25, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
ALKBH8 promotes acute myeloid leukemia progression by coupling codon-dependent translation elongation to mRNA
Songyu Li1, Yunguang Hong2, Songze Deng3
1Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Guangdong, Zhanjiang, China; Zhanjiang Key Laboratory of Leukemia Pathogenesis and Targeted Therapy Research, Zhanjiang, Guangdong, China.
Abstract:
Dysregulated mRNA translation is a critical driver of acute myeloid leukemia (AML) progression. While translation initiation is extensively studied, mechanisms governing translation elongation in AML remain unclear. Here, we show that the RNA methyltransferase ALKBH8 is overexpressed in patients with AML and correlates with poor prognosis. ALKBH8 is required for the proliferation and leukemogenic capacity of human and murine AML cells in vitro and in vivo. Mechanistically, ALKBH8 promotes translation-coupled mRNA stabilization via its methyltransferase domain. Loss of ALKBH8 induces ribosome pausing and preferentially destabilizes transcripts enriched in adenine-ending codons. Specifically, ALKBH8 regulates the expression of the DNA repair gene BRCA1 in a codon-dependent manner, supporting homologous recombination and cell survival. Moreover, ALKBH8 depletion sensitizes AML cells to the PARP inhibitor olaparib. Collectively, our study reveals a codon-specific mechanism of ALKBH8-mediated translation, highlighting the ALKBH8-BRCA1 axis as a potential target for therapeutic intervention.
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