Epigenetic activation of O-linked β-N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia

Abstract Background: Overriding the differentiation blockage in acute myeloid leukemia (AML) is the most successful mode-of-action in leukemia therapy – now curing the vast majority of patients with acute promyelocytic leukemia (APL) using all-trans retinoic acid (ATRA)-based regimens. Similar approaches in other leukemia subtypes, such as IDH1/2-mutated AML, are under active investigation. We herein present successful release of the differentiation blockage upon treatment with the natural (−)-Δ9-Tetrahydrocannabinol isomer dronabinol in vitro and in vivo. Methods: Cellular maturation and differentiation were