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

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
Blood, 15 September 2007, Vol. 110, No. 6, pp. 2084-2091.
Prepublished online as a Blood First Edition Paper on May 30, 2007; DOI 10.1182/blood-2006-12-060970.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Table and Figures
Right arrow All Versions of this Article:
blood-2006-12-060970v1
110/6/2084    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 Bornhauser, B. C.
Right arrow Articles by Bourquin, J.-P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bornhauser, B. C.
Right arrow Articles by Bourquin, J.-P.
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

Low-dose arsenic trioxide sensitizes glucocorticoid-resistant acute lymphoblastic leukemia cells to dexamethasone via an Akt-dependent pathway

Beat C. Bornhauser1, Laura Bonapace1, Dan Lindholm2, Rodrigo Martinez2, Gunnar Cario3, Martin Schrappe3, Felix K. Niggli1, Beat W. Schäfer1, and Jean-Pierre Bourquin1

1 Department of Oncology, Children's Hospital, University of Zurich, Zurich, Switzerland; 2 Department of Neuroscience, Biomedical Center, University of Uppsala, Uppsala, Sweden; 3 Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

Incorporation of apoptosis-inducing agents into current therapeutic regimens is an attractive strategy to improve treatment for drug-resistant leukemia. We tested the potential of arsenic trioxide (ATO) to restore the response to dexamethasone in glucocorticoid (GC)–resistant acute lymphoblastic leukemia (ALL). Low-dose ATO markedly increased in vitro GC sensitivity of ALL cells from T-cell and precursor B-cell ALL patients with poor in vivo response to prednisone. In GC-resistant cell lines, this effect was mediated, at least in part, by inhibition of Akt and affecting downstream Akt targets such as Bad, a proapoptotic Bcl-2 family member, and the X-linked inhibitor of apoptosis protein (XIAP). Combination of ATO and dexamethasone resulted in increased Bad and rapid down-regulation of XIAP, while levels of the antiapoptotic regulator Mcl-1 remained unchanged. Expression of dominant-active Akt, reduction of Bad expression by RNA interference, or overexpression of XIAP abrogated the sensitizing effect of ATO. The inhibitory effect of XIAP overexpression was reduced when the Akt phosphorylation site was mutated (XIAP-S87A). These data suggest that the combination of ATO and glucocorticoids could be advantageous in GC-resistant ALL and reveal additional targets for the evaluation of new antileukemic agents.


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
Sponsor: Genentech BioOncology and and Biogen Idec
Blood Online is supported in part by
Genentech BioOncology and Biogen Idec
  Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020