Mutations in IDH1/2 result in 2-HG production and inhibition of TET2 function. Mutant IDH1 and IDH2 use the aKG produced by their wild-type counterpart as a substrate to produce the oncometabolite 2-HG, which in turns acts as a competitive inhibitor of TET2, thereby blocking the DNA hydroxymethylation pathway, resulting in an increase in the levels of methylated cytosine.