Since epigenetic reprogramming (e.g., by inhibition of the demethylase LSD1) has been shown to unlock the ATRA-induced therapeutic response in non-APL AML (Schenk et al., 2012), it might well be that ATRA/AZA/PGZ treatment also activates the ATRA-driven differentiation pathway by modifying the epigenetic state of leukemic cells. This evidence concerns the gene MBD2 and acute promyelocytic leukemia.