Format

Send to

Choose Destination
Blood. 2010 Sep 30;116(13):2324-31. doi: 10.1182/blood-2010-01-261040. Epub 2010 Jun 23.

Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein.

Author information

1
Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Blindern, Oslo, Norway.

Abstract

Treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid and/or arsenic trioxide represents a paradigm in targeted cancer therapy because these drugs cause clinical remission by affecting the stability of the fusion oncoprotein promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARA). The authors of previous studies have implicated the ubiquitin-proteasome pathway as the main mechanism involved in therapy-induced PML/RARA degradation. Here we have investigated a role of autophagy, a protein degradation pathway that involves proteolysis of intracellular material within lysosomes. We found that both all-trans retinoic acid and arsenic trioxide induce autophagy via the mammalian target of rapamycin pathway in APL cells and that autophagic degradation contributes significantly both to the basal turnover as well as the therapy-induced proteolysis of PML/RARA. In addition, we observed a correlation between autophagy and therapy-induced differentiation of APL cells. Given the central role of the PML/RARA oncoprotein in APL pathogenesis, this study highlights an important role of autophagy in the development and treatment of this disease.

PMID:
20574048
DOI:
10.1182/blood-2010-01-261040
[Indexed for MEDLINE]
Free full text

Publication type, MeSH terms, Substances

Publication type

MeSH terms

Substances

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center