Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 1 March 2008, Vol. 111, No. 5, pp. 2866-2877.
Prepublished online as a Blood First Edition Paper on January 8, 2008; DOI 10.1182/blood-2007-07-103242.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Tables
Right arrow All Versions of this Article:
blood-2007-07-103242v1
111/5/2866    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gausdal, G.
Right arrow Articles by Døskeland, S. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gausdal, G.
Right arrow Articles by Døskeland, S. O.
Related Collections
Right arrow Neoplasia
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

NEOPLASIA

Abolition of stress-induced protein synthesis sensitizes leukemia cells to anthracycline-induced death

Gro Gausdal1,2, Bjørn Tore Gjertsen2,3, Emmet McCormack2, Petra Van Damme4,5, Randi Hovland6, Camilla Krakstad1, Øystein Bruserud2,3, Kris Gevaert4,5, Joël Vandekerckhove4,5, and Stein Ove Døskeland1

1 Department of Biomedicine, University of Bergen, Bergen, Norway; 2 Institute of Medicine, Hematology Section and 3 Department of Internal Medicine, Haukeland University Hospital, Bergen, Norway; 4 Department of Medical Protein Research, Flanders Institute for Biotechnology (VIB), Ghent, Belgium; 5 Department of Biochemistry, Ghent University, Ghent, Belgium; and 6 Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

Anthracycline action has been thought to involve the neosynthesis of proapoptotic gene products and to therefore depend on protein synthesis for optimal effect. We found that inhibition of general, but not rapamycin-sensitive (cap-dependent), protein synthesis in the preapoptotic period enhanced anthracycline-induced acute myelogenous leukemia (AML) cell death, both in vitro and in several animal AML models. Pre-apoptotic anthracycline-exposed AML cells had altered translational specificity, with enhanced synthesis of a subset of proteins, including endoplasmatic reticulum chaperones. The altered translational specificity could be explained by perturbation (protein degradation, truncation, or dephosphorylation) of the cap-dependent translation initiation machinery and of proteins control-ing translation of specific mRNAs. We propose that judiciously timed inhibition of cap-independent translation is considered for combination therapy with anthracyclines in AML.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020