Remarkably, α-KG levels are unchanged in mutant IDH AML and glioma (Dang et al., 2009; Gross et al., 2010), and it is now clear that 2-HG-mediated inhibition of 2-OG-dependent dioxygenases is the dominant mechanism by which IDH mutations are oncogenic (Xu et al., 2011). The gene discussed is IDH2; the disease is central nervous system cancer.