Article
Disabling Uncompetitive Inhibition of Oncogenic IDH Mutations Drives Acquired Resistance.
Cancer discovery - 9 Jan 2023
Lyu Junhua, Liu Yuxuan, Gong Lihu, Chen Mingyi, Madanat Yazan F, Zhang Yuannyu, Cai Feng, Gu Zhimin, Cao Hui, Kaphle Pranita, Kim Yoon Jung, Kalkan Fatma N, Stephens Helen, Dickerson Kathryn E, Ni Min, Chen Weina, Patel Prapti, Mims Alice S, Borate Uma, Burd Amy, Cai Sheng F, Yin C Cameron, You M James, Chung Stephen S, Collins Robert H, DeBerardinis Ralph J, Liu Xin, Xu Jian
Abstract excerpt
Mutations in IDH genes occur frequently in acute myeloid leukemia (AML) and other human cancers to generate the oncometabolite R-2HG. Allosteric inhibition of mutant IDH suppresses R-2HG production in a subset of patients with AML; however, acquired resistance emerges as a new challenge, and the underlying mechanisms remain incompletely understood. Here we establish isogenic leukemia cells containing common IDH...
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