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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 Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-026203v1 108/13/4156    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 Oncogenes and Tumor Suppressors Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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 From the Institut national de la santé et de la recherche médicale (INSERM) U563–Centre de Physiopathologie Toulouse Purpan (CPTP), Département d'Oncogenèse et Signalisation dans les Cellules Hématopoïétiques, Centre Hospitalier Universitaire (CHU) Purpan–BP3028, Toulouse, France; INSERM U563-CPTP, Département Lipoprotéines et Médiateurs Lipidiques, CHU Purpan–BP3028, Toulouse, France; Plateau technique d'histopathologie expérimentale, Institut Fédératif de Recherche (IFR) 30, CHU Purpan–BP3028, Toulouse, France; and Service d'hématologie, Centre Hospitalier Universitaire Purpan, Toulouse, France. The mammalian target of rapamycin (mTOR) is emerging as a promising target for antitumor therapy. However, the mechanism that contributes to its regulation in B lymphomas remains unknown. This study shows that in follicular lymphoma (FL) cells, mTOR is active because the cells displayed rapamycin-sensitive phosphorylation of p70S6 kinase and 4E-BP1. Moreover, immunohistochemistry applied on lymph node tissue sections obtained from patients with FL revealed that, in most cases, p70S6 kinase was highly phosphorylated compared to normal tonsillar tissue. In FL cells, mTOR was under control of both phospholipase D (PLD) and phosphatidylinositol 3-kinase (PI3K). Moreover, we demonstrated that Syk plays a central role in mTOR activation because we found that both expression and activity are elevated compared to normal or chronic lymphocytic leukemia B cells. We also provide evidence 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 has a critical function in FL survival, and therefore, that Syk could be a promising new target for B-lymphoma therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    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] This article has been cited by other articles: S.-W. Kim, D. Rai, M. R. McKeller, and R. C. T. Aguiar Rational combined targeting of phosphodiesterase 4B and SYK in DLBCL Blood, June 11, 2009; 113(24): 6153 - 6160. [Abstract] [Full Text] [PDF] R. M. Young, I. R. Hardy, R. L. Clarke, N. Lundy, P. Pine, B. C. Turner, T. A. Potter, and Y. Refaeli Mouse models of non-Hodgkin lymphoma reveal Syk as an important therapeutic target Blood, March 12, 2009; 113(11): 2508 - 2516. [Abstract] [Full Text] [PDF] D. A. Rizzieri, E. Feldman, J. F. DiPersio, N. Gabrail, W. Stock, R. Strair, V. M. Rivera, M. 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Recher A critical role for Lyn in acute myeloid leukemia Blood, February 15, 2008; 111(4): 2269 - 2279. [Abstract] [Full Text] [PDF] L. Leseux, G. Laurent, C. Laurent, M. Rigo, A. Blanc, D. Olive, and C. Bezombes PKC {zeta} mTOR pathway: a new target for rituximab therapy in follicular lymphoma Blood, January 1, 2008; 111(1): 285 - 291. [Abstract] [Full Text] [PDF] S. Luangdilok, C. Box, L. Patterson, W. Court, K. Harrington, L. Pitkin, P. Rhys-Evans, P. O-charoenrat, and S. Eccles Syk Tyrosine Kinase Is Linked to Cell Motility and Progression in Squamous Cell Carcinomas of the Head and Neck Cancer Res., August 15, 2007; 67(16): 7907 - 7916. [Abstract] [Full Text] [PDF]

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