Retinoid receptor signaling and autophagy in acute promyelocytic leukemia.

Abstract

Retinoids 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.

• Authors: Nina Orfali, Sharon L McKenna, Mary R Cahill, Lorraine J Gudas, Nigel P Mongan
• Journal: Experimental cell research (Exp Cell Res) Vol. 324 Issue 1 Pg. 1-12 (May 15 2014) ISSN: 1090-2422 [Electronic] United States
• PMID: 24694321 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Receptors, Retinoic Acid
• Retinoids

Topics

• Animals
• Autophagy (genetics)
• Cell Differentiation (genetics)
• Hematopoiesis (physiology)
• Humans
• Leukemia, Promyelocytic, Acute (drug therapy, genetics, pathology)
• Receptors, Retinoic Acid (physiology)
• Retinoids (therapeutic use)
• Signal Transduction (physiology)