Retinoic acid (RA) signaling pathways regulate fundamental biological processes, such as cell proliferation, development, differentiation, and apoptosis. Retinoid receptors (RARs and RXRs) are ligand-dependent transcription factors. All-trans retinoic acid (ATRA) is the principal endogenous ligand for the retinoic acid receptor alpha (RARA) and is produced by the enzymatic oxidation of dietary vitamin A, whose deficiency is associated with several pathological conditions. Differentiation therapy using ATRA revolutionized the outcome of acute promyelocytic leukemia (APL), although attempts to replicate these results in other cancer types have been met with more modest results. A better knowledge of RA signaling in different leukemia contexts is required to improve initial designs. Here, we will review the RA signaling pathway in normal and malignant hematopoiesis, and will discuss the advantages and the limitations related to retinoid therapy in acute myeloid leukemia.
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