Figure 2.

In leukemic stem cells (LSC) the genes that program differentiation are silenced by DNA methylation (Cme), methylation of H327 (Kme³) and/or methylation of H3K9 (Kme²). Treatment of LSCs with an inhibitor of DNA methylation, an inhibitor of H3H27 methylation and/or an inhibitor of H3K9 methylation leads to reactivation of genes that program differentiation and loss of self-renewal capacity of the leukemic cells (LC). The cellular intrinsic enzymatic demethylating action of the TET and JHDM can also lead to activation of differentiation and loss of self-renewal capacity of the LSC. It is possible that this intrinsic enzymatic mechanism can increase the effectiveness of the epigenetic therapy the treatment for AML.