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Blood, 1 August 2005, Vol. 106, No. 3, pp. 1021-1030. Prepublished online as a Blood First Edition Paper on April 12, 2005; DOI 10.1182/blood-2004-11-4512. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 2004-11-4512v1 106/3/1021    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 Klein, B. Search for Related Content PubMed PubMed Citation Articles by Moreaux, J. Articles by Klein, B. Related Collections Immunobiology Neoplasia Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature Jérôme Moreaux, Friedrich W. Cremer, Thierry Reme, Marc Raab, Karene Mahtouk, Philine Kaukel, Veronique Pantesco, John De Vos, Eric Jourdan, Anna Jauch, Eric Legouffe, Marion Moos, Genevieve Fiol, Hartmut Goldschmidt, Jean François Rossi, Dirk Hose, and Bernard Klein From INSERM U475 and the Unit for Cellular Therapy, CHU Montpellier, Hopital St Eloi, and the Clinical Hematology Department, CHU Montpellier, Hopital Lapeyronie, Montpellier, France; Medizinische Klinik und Poliklinik V, and the Institut für Humangenetik, Universitätsklinikum Heidelberg, Heidelberg, Germany; and the Internal Medicine Department B, CHU de Nîmes, Nîmes, France. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) have been shown to promote multiple myeloma (MM) cell growth. We show that the main site of production for BAFF and APRIL is the bone marrow (BM) environment, and that production is mainly by monocytes and neutrophils. In addition, osteoclasts produce very high levels of APRIL, unlike BM stromal cells. Myeloma cells (MMCs) express TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor), the receptor of BAFF/APRIL, at varying levels. TACI expression is a good indicator of a BAFF-binding receptor. Expression data of purified MMCs from 65 newly diagnosed patients have been generated using Affymetrix microarrays and were analyzed by supervised clustering of groups with higher (TACIhi) versus lower (TACIlo) TACI expression levels. Patients in the TACIlo group had clinical parameters associated with bad prognosis. A set of 659 genes was differentially expressed between TACIhi and TACIlo MMCs. This set makes it possible to efficiently classify TACIhi and TACIlo MMCs in an independent cohort of 40 patients. TACIhi MMCs displayed a mature plasma cell gene signature, indicating dependence on the BM environment. In contrast, the TACIlo group had a gene signature of plasmablasts, suggesting an attenuated dependence on the BM environment. Taken together, our findings suggest using gene expression profiling to identify the group of patients who might benefit most from treatment with BAFF/APRIL inhibitors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: APRIL showers cause CLL and myeloma to flower John Shaughnessy, Jr Blood 2005 106: 766-767. [Full Text] [PDF] This article has been cited by other articles: D. Hose, J. Moreaux, T. Meissner, A. Seckinger, H. Goldschmidt, A. Benner, K. Mahtouk, J. Hillengass, T. Reme, J. De Vos, et al. Induction of angiogenesis by normal and malignant plasma cells Blood, July 2, 2009; 114(1): 128 - 143. [Abstract] [Full Text] [PDF] M. Gupta, S. R. Dillon, S. C. Ziesmer, A. L. Feldman, T. E. Witzig, S. M. Ansell, J. R. Cerhan, and A. J. 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MacLennan Response to the Comments on "Dendritic Cells and Monocyte/Macrophages That Create the IL-6/APRIL-Rich Lymph Node Microenvironment Where Plasmablasts Mature" J. Immunol., May 1, 2009; 182(9): 5160 - 5160. [Full Text] [PDF] D. Hose, T. Reme, T. Meissner, J. Moreaux, A. Seckinger, J. Lewis, V. Benes, A. Benner, M. Hundemer, T. Hielscher, et al. Inhibition of aurora kinases for tailored risk-adapted treatment of multiple myeloma Blood, April 30, 2009; 113(18): 4331 - 4340. [Abstract] [Full Text] [PDF] A. Geffroy-Luseau, G. Jego, R. Bataille, L. Campion, and C. Pellat-Deceunynck Osteoclasts support the survival of human plasma cells in vitro Int. Immunol., June 1, 2008; 20(6): 775 - 782. [Abstract] [Full Text] [PDF] D. L. Langat, D. A. Wheaton, J. S. Platt, T. Sifers, and J. S. Hunt Signaling Pathways for B Cell-Activating Factor (BAFF) and a Proliferation-Inducing Ligand (APRIL) in Human Placenta Am. J. Pathol., May 1, 2008; 172(5): 1303 - 1311. [Abstract] [Full Text] [PDF] K. Mahtouk, D. Hose, J. De Vos, J. Moreaux, M. Jourdan, J. F. Rossi, T. Reme, H. Goldschmidt, and B. Klein Input of DNA Microarrays to Identify Novel Mechanisms in Multiple Myeloma Biology and Therapeutic Applications Clin. Cancer Res., December 15, 2007; 13(24): 7289 - 7295. [Abstract] [Full Text] [PDF] J. R. Darce, B. K. Arendt, X. Wu, and D. F. Jelinek Regulated Expression of BAFF-Binding Receptors during Human B Cell Differentiation J. Immunol., December 1, 2007; 179(11): 7276 - 7286. [Abstract] [Full Text] [PDF] P. Neri, S. Kumar, M. T. Fulciniti, S. Vallet, S. Chhetri, S. Mukherjee, Y. Tai, D. Chauhan, P. Tassone, S. Venuta, et al. Neutralizing B-Cell Activating Factor Antibody Improves Survival and Inhibits Osteoclastogenesis in a Severe Combined Immunodeficient Human Multiple Myeloma Model Clin. Cancer Res., October 1, 2007; 13(19): 5903 - 5909. [Abstract] [Full Text] [PDF] Y.-T. Tai, M. Fulciniti, T. Hideshima, W. Song, M. Leiba, X.-F. Li, M. Rumizen, P. Burger, A. Morrison, K. Podar, et al. Targeting MEK induces myeloma-cell cytotoxicity and inhibits osteoclastogenesis Blood, September 1, 2007; 110(5): 1656 - 1663. [Abstract] [Full Text] [PDF] H. A. Minges Wols, J. A. Ippolito, Z. Yu, J. L. Palmer, F. A. White, P. T. Le, and P. L. Witte The effects of microenvironment and internal programming on plasma cell survival Int. Immunol., July 2, 2007; (2007) dxm051v1. [Abstract] [Full Text] [PDF] J. Moreaux, D. Hose, M. Jourdan, T. Reme, M. Hundemer, M. Moos, N. Robert, P. Moine, J. De Vos, H. Goldschmidt, et al. TACI expression is associated with a mature bone marrow plasma cell signature and C-MAF overexpression in human myeloma cell lines Haematologica, June 1, 2007; 92(6): 803 - 811. [Abstract] [Full Text] [PDF] K. Mahtouk, D. Hose, P. Raynaud, M. Hundemer, M. Jourdan, E. Jourdan, V. Pantesco, M. Baudard, J. De Vos, M. Larroque, et al. Heparanase influences expression and shedding of syndecan-1, and its expression by the bone marrow environment is a bad prognostic factor in multiple myeloma Blood, June 1, 2007; 109(11): 4914 - 4923. [Abstract] [Full Text] [PDF] K. L.M. Boylan, M. A. Gosse, S. E. Staggs, S. Janz, S. Grindle, G. S. Kansas, and B. G. Van Ness A Transgenic Mouse Model of Plasma Cell Malignancy Shows Phenotypic, Cytogenetic, and Gene Expression Heterogeneity Similar to Human Multiple Myeloma Cancer Res., May 1, 2007; 67(9): 4069 - 4078. [Abstract] [Full Text] [PDF] Y. Tanaka, M. Abe, M. Hiasa, A. Oda, H. Amou, A. Nakano, K. Takeuchi, K. Kitazoe, S. Kido, D. Inoue, et al. Myeloma Cell-Osteoclast Interaction Enhances Angiogenesis Together with Bone Resorption: A Role for Vascular Endothelial Cell Growth Factor and Osteopontin Clin. Cancer Res., February 1, 2007; 13(3): 816 - 823. [Abstract] [Full Text] [PDF] A. Chiu, W. Xu, B. He, S. R. Dillon, J. A. Gross, E. Sievers, X. Qiao, P. Santini, E. Hyjek, J.-w. 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Cancer Res., July 1, 2006; 66(13): 6675 - 6682. [Abstract] [Full Text] [PDF] S. F. Elsawa, A. J. Novak, D. M. Grote, S. C. Ziesmer, T. E. Witzig, R. A. Kyle, S. R. Dillon, B. Harder, J. A. Gross, and S. M. Ansell B-lymphocyte stimulator (BLyS) stimulates immunoglobulin production and malignant B-cell growth in Waldenstrom macroglobulinemia Blood, April 1, 2006; 107(7): 2882 - 2888. [Abstract] [Full Text] [PDF] T. Matsumoto and M. Abe Myeloma-Bone Interaction: A Vicious Cycle IBMS BoneKEy, March 1, 2006; 3(3): 8 - 14. [Abstract] [Full Text] [PDF]

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