Collectively, these observations highlight a complex and ill-understood relationship between retinoic acid signaling, normal myeloid differentiation, leukemic transformation and a potential benefit of ATRA signaling in AML cells, where RARA-mediated basal repression of retinoic acid signaling or its ATRA-triggered activation, seem to be a central theme, independently from fusion proteins. The gene discussed is RARA; the disease is acute myeloid leukemia.