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Blood, 1 January 2008, Vol. 111, No. 1, pp. 285-291. Prepublished online as a Blood First Edition Paper on September 12, 2007; DOI 10.1182/blood-2007-04-085092. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-04-085092v1 111/1/285    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Leseux, L. Articles by Bezombes, C. Search for Related Content PubMed PubMed Citation Articles by Leseux, L. Articles by Bezombes, C. Related Collections Neoplasia Signal Transduction Immunotherapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA PKC –mTOR pathway: a new target for rituximab therapy in follicular lymphoma Ludivine Leseux1, Guy Laurent1,2, Camille Laurent3, Maxime Rigo1, Amandine Blanc1, Daniel Olive4, and Christine Bezombes1 1 INSERM, Unite 563, Centre de Physiopathologie de Toulouse Purpan, Université Toulouse III Paul-Sabatier, Toulouse; 2 Service d'hématologie, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; 3 Service d'anatomie et cytologie pathologiques, CHU Purpan, Toulouse; and 4 Immunologie des Tumeurs, Institut Paoli-Calmettes, Faculté de Médecine de Marseille, Université de la Méditerranée, Marseille, France Previous studies have documented that, in malignant B cells, rituximab elicits a complex and not yet totally understood signaling network contributing to its antitumor effect. In this context, we investigated the role of protein kinase C (PKC), an atypical PKC isoform, in the cellular response to rituximab. We found that follicular lymphoma cells displayed an increase in PKC expression and activity levels, compared with nonmalignant B cells, and that this enzyme was a critical regulator of the classical MAPK module by stimulating Raf-1 kinase activity. PKC appeared to be a significant contributor of abnormal mTOR regulation in follicular lymphoma cells through a MAPK-dependent mechanism. Rituximab was found to inhibit the PKC/MAPK/mTOR module in these cells but not in other B-cell lymphomas. Importantly, the expression of a constitutively active form of PKC resulted in an efficient protection of these cells toward rituximab. Altogether, our study describes a new regulatory component of mTOR pathway in follicular cell lymphoma and demonstrates that PKC is a target for rituximab. Therefore, PKC could represent an important parameter for rituximab efficacy and a promising target for future targeted therapy in follicular lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The rituximab-PKC/Raf-1/mTOR connection Benjamin Bonavida Blood 2008 111: 5-6. [Full Text] [PDF] This article has been cited by other articles: K. B. Adler and S. Matalon Highlights of the August Issue Am. J. Respir. Cell Mol. Biol., August 1, 2009; 41(2): 125 - 126. [Full Text] [PDF] J. Gertner-Dardenne, C. Bonnafous, C. Bezombes, A.-H. Capietto, V. Scaglione, S. Ingoure, D. Cendron, E. Gross, J.-F. Lepage, A. Quillet-Mary, et al. Bromohydrin pyrophosphate enhances antibody-dependent cell-mediated cytotoxicity induced by therapeutic antibodies Blood, May 14, 2009; 113(20): 4875 - 4884. [Abstract] [Full Text] [PDF] M. Bendandi Aiming at a Curative Strategy for Follicular Lymphoma CA Cancer J Clin, September 1, 2008; 58(5): 305 - 317. [Abstract] [Full Text] [PDF]

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