Retinoid receptor signaling and autophagy in acute promyelocytic leukemia Review uri icon

Overview

MeSH Major

  • Autophagy
  • Leukemia, Promyelocytic, Acute
  • Receptors, Retinoic Acid

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 RARĪ± 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. RARĪ± 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.

publication date

  • May 15, 2014

Research

keywords

  • Review

Identity

Language

  • eng

PubMed Central ID

  • PMC4047711

Digital Object Identifier (DOI)

  • 10.1016/j.yexcr.2014.03.018

PubMed ID

  • 24694321

Additional Document Info

start page

  • 1

end page

  • 12

volume

  • 324

number

  • 1