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 December 2006, Vol. 108, No. 13, pp. 4156-4162.
Prepublished online as a Blood First Edition Paper on August 15, 2006; DOI 10.1182/blood-2006-05-026203.


This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
blood-2006-05-026203v1
108/13/4156    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 Leseux, L.
Right arrow Articles by Bezombes, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leseux, L.
Right arrow Articles by Bezombes, C.
Related Collections
Right arrowRelated Article in Blood Online
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  |  Next Article next article arrow

Submitted May 30, 2006
Accepted July 28, 2006

Syk-dependent mTOR activation in follicular lymphoma cells

Ludivine Leseux, Safouane M Hamdi, Talal al Saati, Florence Capilla, Christian Recher, Guy Laurent, and Christine Bezombes*

Inserm U563-PTP Departement d'Oncogenese et Signalisation dans les Cellules Hematopoietiques, France
INSERM U563 - CPTP, Departement Lipoproteines et Mediateurs Lipidiques, CHU Purpan, France
Plateau technique d'histopathologie experimentale, IFR 30, CHU Purpan, Toulouse cedex 3, France
Service d'hematologie, Centre Hospitalier Universitaire Purpan, Place Dr Baylac, France

* Corresponding author; email: christine.bezombes-cagnac{at}toulouse.inserm.fr.

The mammalian Target of Rapamycin (mTOR) is emerging as a promising target for anti-tumor therapy. However, the mechanism which contributes to its regulation in B lymphomas remains unknown. This study shows that in follicular lymphoma (FL) cells, mTOR is active as they displayed rapamycin-sensitive phosphorylation of p70S6 kinase and 4E-BP1. Moreover, immunohistochemistry applied on lymph node tissue sections obtained from FL patients revealed that, in most cases, p70S6 kinase was highly phosphorylated, compared to normal tonsil. In FL cells, mTOR was found to be under control of both phospholipase D (PLD) and phosphatidylinositol 3-kinase (PI3K). Moreover, we demonstrated that Syk plays a central role in mTOR activation as we found that both expression and activity are elevated compared to normal or chronic lymphocytic leukemia B cells. We also provide evidences that Syk operates through PLD- and PI3K-independent pathways. Finally, Syk inhibition by piceatannol or by siRNA plasmids resulted in a potent inhibition of mTOR activity in FL cells, as well as in mantle cell lymphoma, Burkitt lymphoma and diffuse large B-cell lymphoma. These findings suggest that the Syk-mTOR pathway plays a critical function in follicular lymphoma survival, and therefore, that Syk could be a promising new target for B-lymphoma therapy.


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?

Related Article in Blood Online:

Syk-driven mTOR in lymphoma-complimentary targets?
Francis J. Giles
Blood 2006 108: 3957-3958. [Full Text] [PDF]





 click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020