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Blood, 15 April 2004, Vol. 103, No. 8, pp. 3148-3157. Prepublished online as a Blood First Edition Paper on December 4, 2003; DOI 10.1182/blood-2003-06-1984. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-1984v1 103/8/3148    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 Moreaux, J. Articles by Tarte, K. Search for Related Content PubMed PubMed Citation Articles by Moreaux, J. Articles by Tarte, K. Related Collections Neoplasia Apoptosis Signal Transduction Gene Expression Genomics Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone Jérôme Moreaux, Eric Legouffe, Eric Jourdan, Philippe Quittet, Thierry Rème, Cécile Lugagne, Philippe Moine, Jean-François Rossi, Bernard Klein, and Karin Tarte From Institut National de la Santé et de la Recherche Médicale (INSERM) U475 and Unité de Thérapie Cellulaire, Centre Hospitalier Universitaire (CHU) Montpellier, Hôpital St Eloi, and the Service d'Hématologie et Oncologie Médicale, CHU Montpellier, Hôpital Lapeyronie, Montpellier, France; and the Service de Médecine Interne B, CHU de Nîmes, France. Identification of growth factors in neoplasias may be a target for future therapies by blocking either growth factor receptor interaction or the induced pathway. Using gene expression profiling, we identified overexpression of 2 receptors for a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) in malignant plasma cells compared with normal plasma cells. APRIL and BAFF are involved in a variety of tumor and autoimmune diseases, including B-cell malignancies. We confirmed the expression of BAFF and APRIL receptors (B-cell maturation antigen [BCMA], transmembrane activator and calcium modulator and cyclophilin ligand interactor [TACI], and BAFF-R) in a majority of 13 myeloma cell lines and in the purified primary myeloma cells of 11 patients. APRIL and BAFF were potent survival factors for exogenous cytokine-dependent myeloma cell lines and were autocrine growth factors for the RPMI8226 and L363 autonomously growing cell lines. These factors activated nuclear factor (NF)–B, phosphatidylinositol-3 (PI-3) kinase/AKT, and mitogen-activated protein kinase (MAPK) kinase pathways and induced a strong up-regulation of the Mcl-1 and Bcl-2 antiapoptotic proteins in myeloma cells. BAFF or APRIL was also involved in the survival of primary myeloma cells cultured with their bone-marrow environment, and protected them from dexamethasone (DEX)–induced apoptosis. Finally, the serum levels of BAFF and APRIL were increased about 5-fold in patients with multiple myeloma (MM) as compared with healthy donors. Altogether, these data suggest that APRIL/BAFF inhibitors may be of clinical value in MM. (Blood. 2004;103:3148-3157) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S.-H. Kuo, P.-Y. Yeh, L.-T. Chen, M.-S. Wu, C.-W. Lin, K.-H. Yeh, Y.-S. Tzeng, J.-Y. Chen, P.-N. Hsu, J.-T. Lin, et al. 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