IDH3 regulates citrate homeostasis to control metabolic fitness and venetoclax resistance of AML stem cells
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The authors investigate the role of isocitrate dehydrogenase 3 (IDH3) in regulating metabolic fitness and resistance to venetoclax in acute myeloid leukemia (AML) stem cells. They find that IDH3 is crucial for maintaining the tricarboxylic acid (TCA) cycle activity in leukemic stem cells, and its downregulation leads to a metabolic crisis that enhances susceptibility to BCL2 inhibition. The study suggests that targeting the IDH3A-citrate axis could be a potential strategy to overcome treatment resistance in AML patients.
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