MTOR and cancer: In acute myeloid leukemia and gliomas, cancer-associated mutations in the TCA enzymes IDH1 and IDH2 lead to the production of 2HG from α-KG.454 This abnormal generation of 2HG results in mTOR activation through the inhibition of KDM4A, an α-KG-dependent lysine demethylase that stabilizes the mTOR suppressor DEPTOR.