The drug mechanism has long been attributed to their combined ability to induce degradation of the disease-causing oncoprotein promyelocytic leukemia-retinoic acid receptor α (PML-RARα) by acting on the two fusion partners; ATO covalently interacts with Cys in PML, whereas ATRA activates RARα receptor to induce cell differentiation10–12. The gene discussed is PML; the disease is leukemia.