2025/05/27 by Shunlei Duan, Karl Agger, Jan‐Erik Messling +18 · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · #Acute Myeloid Leukemia Research #Drug Transport and Resistance Mechanisms #Protein Degradation and Inhibitors
paper · pdf · doi:10.1038/s41467-025-59969-8
openalex publication_date 2025/05/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
The lack of curative therapies for acute myeloid leukaemia (AML) remains an ongoing challenge despite recent advances in the understanding of the molecular basis of the disease. Here we identify the WNK1-OXSR1/STK39 pathway as a previously uncharacterised dependency in AML. We show that genetic depletion and pharmacological inhibition of WNK1 or its downstream phosphorylation targets OXSR1 and STK39 strongly reduce cell proliferation and induce apoptosis in leukaemia cells in vitro and in vivo. Furthermore, we show that the WNK1-OXSR1/STK39 pathway controls mTORC1 signalling via regulating amino acid uptake through a mechanism involving the phosphorylation of amino acid transporters, such as SLC38A2. Our findings underscore an important role of the WNK1-OXSR1/STK39 pathway in regulating amino acid uptake and driving AML progression.