 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 . 
 An important pathophysiological mechanism of leukemogenesis in AML <a href='drop_aux' title='1'><mark>is</mark></a>the epigenetic induction of dedifferentiation by genetic mutations <a href='null_relcl' title='2'><mark>that</mark></a>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 <a href='uninflect' title='3'><mark>inhibits</mark></a> 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 . 
An important pathophysiological mechanism of leukemogenesis in AML da epigenetic induction of dedifferentiation by genetic mutations alter the function of epigenetic enzymes , such as tdaDNA demethylase TET2 and the metabolic enzymes IDH1 and IDH2 , which lead to thdaeneration of a novel oncometabolite , D @-@ 2 @-@ hydroxyglutarate , which inhibit thedativity of epigenetic enzymes such as TET2 . The daothesis is dat such epigenetic mutations lead to the sdancing of tumor suppressor genes and / or the acdaation of proto @-@ oncogenes .