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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  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. 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: M. El-Salem, P. N. Raghunath, M. Marzec, X. Liu, M. Kasprzycka, E. Robertson, and M. A. Wasik Activation of mTORC1 Signaling Pathway in AIDS-Related Lymphomas Am. J. Pathol., August 1, 2009; 175(2): 817 - 824. [Abstract] [Full Text] [PDF] 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] K. R. Calvo, B. Dabir, A. Kovach, C. Devor, R. Bandle, A. Bond, J. H. Shih, and E. S. Jaffe IL-4 protein expression and basal activation of Erk in vivo in follicular lymphoma Blood, November 1, 2008; 112(9): 3818 - 3826. [Abstract] [Full Text] [PDF] D. A. Rizzieri, E. Feldman, J. F. DiPersio, N. Gabrail, W. Stock, R. Strair, V. M. Rivera, M. Albitar, C. L. Bedrosian, and F. J. Giles A Phase 2 Clinical Trial of Deforolimus (AP23573, MK-8669), a Novel Mammalian Target of Rapamycin Inhibitor, in Patients with Relapsed or Refractory Hematologic Malignancies Clin. Cancer Res., May 1, 2008; 14(9): 2756 - 2762. [Abstract] [Full Text] [PDF] L. Chen, S. Monti, P. Juszczynski, J. Daley, W. Chen, T. E. Witzig, T. M. Habermann, J. L. Kutok, and M. A. Shipp SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma Blood, February 15, 2008; 111(4): 2230 - 2237. [Abstract] [Full Text] [PDF] M. Marzec, X. Liu, M. Kasprzycka, A. Witkiewicz, P. N. Raghunath, M. El-Salem, E. Robertson, N. Odum, and M. A. Wasik IL-2- and IL-15-induced activation of the rapamycin-sensitive mTORC1 pathway in malignant CD4+ T lymphocytes Blood, February 15, 2008; 111(4): 2181 - 2189. [Abstract] [Full Text] [PDF] C. Dos Santos, C. Demur, V. Bardet, N. Prade-Houdellier, B. Payrastre, and C. 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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