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Altered Oxidative Phosphorylation Confers Vulnerability on IDH1-Mutant Leukemia Cells: Is This Therapeutically
1Ajax Therapeutics, Inc., Cambridge, Massachusetts.
Summary:
Isocitrate dehydrogenase (IDH)-mutant acute myeloid leukemia (AML) is treatable with inhibitors of mutant IDH and also responds well to combination therapies including venetoclax, but most patients with IDH-mutant AML either never achieve complete remission or relapse because mutant hematopoietic stem cells persist despite treatment. An interesting new study in Blood Cancer Discovery characterizes a specific vulnerability in the mitochondrial oxidative phosphorylation system in preleukemic hematopoietic stem cells from patients with IDH1 mutations that is not present in those with IDH2 mutations; will this susceptibility prove amenable to therapy? See related article by Landberg et al., p. 114 (10).
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