Counteracts Anti-Leukemic and Stem Cell Inhibitory Effects of Retinoic Acid on -ITD/-Driven Acute Myeloid Leukemia Cells.

retinoic acid (atRA) has a dramatic impact on the survival of patients with acute promyelocytic leukemia, but its therapeutic value in other types of acute myeloid leukemia (AML) has so far remained unclear. Given that AML is a stem cell-driven disease, recent studies have addressed the effects of atRA on leukemic stem cells (LSCs). atRA promoted stemness of -driven AML in an -dependent manner but had the opposite effect in -ITD/-driven AML. Overexpression of the stem cell-associated transcription factor predicts a poor prognosis in AML, and is observed in different genetic subtypes, including cytogenetically normal AML. Here, we therefore investigated the effects of in a mouse model for cytogenetically normal AML, which rests on the combined activity of -ITD and mutations. Experimental expression of on this background strongly promoted disease aggressiveness. atRA inhibited leukemia cell viability and stem cell-related properties, and these effects were counteracted by overexpression of . These data further underscore the complexity of the responsiveness of AML LSCs to atRA and point out the need for additional investigations which may lay a foundation for a precision medicine-based use of retinoids in AML.