Retinoid receptor signaling and autophagy in acute promyelocytic leukemia.
AffiliationCork Cancer Research Center, University College Cork, Cork, Ireland; Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA.
Leukemia, Promyelocytic, Acute
Receptors, Retinoic Acid
MetadataShow full item record
CitationRetinoid receptor signaling and autophagy in acute promyelocytic leukemia. 2014, 324 (1):1-12 Exp. Cell Res.
JournalExperimental cell research
AbstractRetinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies.
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