ALKBH8 promotes acute myeloid leukemia progression by coupling codon-dependent translation elongation to mRNA stability
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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BibTeX
@article{li2026alkbh8,
title = {{ALKBH8 promotes acute myeloid leukemia progression by coupling codon-dependent translation elongation to mRNA stability}},
author = {Songyu Li and Yunguang Hong and Songze Deng and Xiang Wu and Zhirong Jia and Yan Liu and Ya Liu and Guocai Wu and Yinhui Chen and Aibing Wu and Xiangwei Gao and Zhanghui Chen},
journal = {Cell Reports},
year = {2026},
month = oct,
doi = {10.1016/j.celrep.2026.118193},
url = {https://linkinghub.elsevier.com/retrieve/pii/S2211124726012726},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - ALKBH8 promotes acute myeloid leukemia progression by coupling codon-dependent translation elongation to mRNA stability
AU - Songyu Li
AU - Yunguang Hong
AU - Songze Deng
AU - Xiang Wu
AU - Zhirong Jia
AU - Yan Liu
AU - Ya Liu
AU - Guocai Wu
AU - Yinhui Chen
AU - Aibing Wu
AU - Xiangwei Gao
AU - Zhanghui Chen
PY - 2026
DA - 2026/10/30
JO - Cell Reports
DO - 10.1016/j.celrep.2026.118193
UR - https://linkinghub.elsevier.com/retrieve/pii/S2211124726012726
AB - 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.
SN - 2211-1247
ER -