This review article provides evidence on the consequences of the treatment with PPARγ ligands, in particular the triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), on the epigenetic/transcriptional events induced by retinoic acid in APL cells, and supports the clinical utility of ATRA/PPARγ-ligand combinations for treating hematological malignancies. This evidence concerns the gene PPARG and acute promyelocytic leukemia.