An important pathophysiological mechanism of leukemogenesis in AML is the epigenetic induction of dedifferentiation by genetic mutations that alter the function of epigenetic enzymes , such as the DNA demethylase TET2 and the metabolic enzymes IDH1 and IDH2 , which lead to the generation of a novel oncometabolite , D @-@ 2 @-@ hydroxyglutarate , which inhibits the activity of epigenetic enzymes such as TET2 . The hypothesis is that such epigenetic mutations lead to the silencing of tumor suppressor genes and / or the activation of proto @-@ oncogenes .