There is strong circumstantial evidence from acute myeloid leukemias (AMLs) that DNA demethylases are the targets of the D2-HG produced by the IDH mutations: AMLs tend to have either the mutations in IDH or mutations in the genes encoding TET enzymes, but not both (Figueroa et al., 2010; Gaidzik et al., 2012). This evidence concerns the gene IDH2 and acute myeloid leukemia.