Article
Dysregulated Lipid Synthesis by Oncogenic IDH1 Mutation Is a Targetable Synthetic Lethal Vulnerability.
Cancer discovery - 6 Feb 2023
Thomas Daniel, Wu Manhong, Nakauchi Yusuke, Zheng Ming, Thompson-Peach Chloe A L, Lim Kelly, Landberg Niklas, Köhnke Thomas, Robinson Nirmal, Kaur Satinder, Kutyna Monika, Stafford Melissa, Hiwase Devendra, Reinisch Andreas, Peltz Gary, Majeti Ravindra
Abstract excerpt
Isocitrate dehydrogenase 1 and 2 (IDH) are mutated in multiple cancers and drive production of (R)-2-hydroxyglutarate (2HG). We identified a lipid synthesis enzyme [acetyl CoA carboxylase 1 (ACC1)] as a synthetic lethal target in mutant IDH1 (mIDH1), but not mIDH2, cancers. Here, we analyzed the metabolome of primary acute myeloid leukemia (AML) blasts and identified an mIDH1-specific reduction in fatty acids....
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