Because IDH1 and IDH2 are enzymes of the Krebs cycle, these findings represent a direct link of TET protein activity to metabolism, especially because low 5-hydroxymethylcytosine levels are found in acute myeloid leukemia patients not only with TET2 loss-of-function mutations but also with IDH2 gain-of-function mutations (20). Here, IDH2 is linked to acute myeloid leukemia.