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Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2002, Vol. 99, No. 10, pp. 3756-3762 NEOPLASIA Interleukin-21 is a growth and survival factor for human myeloma cells Anne-Tove Brenne, Torstein Baade Ro, Anders Waage, Anders Sundan, Magne Borset, and Henrik Hjorth-Hansen From the Department of Cancer Research and Molecular Biology and the Section of Hematology, Department of Environmental Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Interleukin-21 (IL-21) is a recently cloned cytokine with homology to IL-2, IL-4, and IL-15. In this study we examined the effects of IL-21 on human myeloma cells. We found that IL-21 induced proliferation and inhibited apoptosis of the IL-6-dependent human myeloma cell lines ANBL-6, IH-1, and OH-2. The potency of IL-21 was close to that of IL-6 in the OH-2 cell line. Neutralizing antibodies to IL-6 or the IL-6 receptor transducer chain (gp130) did not affect IL-21-induced DNA synthesis, indicating that IL-21-induced proliferation was not mediated through these proteins. Tumor necrosis factor (TNF), another stimulator of myeloma cell growth, up-regulated the expression level of IL-21 receptor (IL-21R), and combinations of TNF and IL-21 gave synergistic effects on myeloma cell proliferation. Furthermore, 4 of 9 purified samples of primary myeloma cells showed a significant increase in DNA synthesis on stimulation of the cells by IL-21. By Western blot analysis, we demonstrated that the intracellular signaling pathways of IL-21 in myeloma cells involved phosphorylation of Jak1, Stat3, and Erk1/2 (p44/42 mitogen-activated protein kinase). IL-21 is a novel growth and survival factor in multiple myeloma and may represent a target for future therapy. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Dien Bard, P. Gelebart, M. Anand, Z. Zak, S. A. Hegazy, H. M. Amin, and R. Lai IL-21 Contributes to JAK3/STAT3 Activation and Promotes Cell Growth in ALK-Positive Anaplastic Large Cell Lymphoma Am. J. Pathol., August 1, 2009; 175(2): 825 - 834. [Abstract] [Full Text] [PDF] A. C. Sprynski, D. Hose, L. Caillot, T. Reme, J. D. Shaughnessy Jr, B. Barlogie, A. Seckinger, J. Moreaux, M. Hundemer, M. Jourdan, et al. The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor Blood, May 7, 2009; 113(19): 4614 - 4626. [Abstract] [Full Text] [PDF] A. Thedrez, C. Harly, A. Morice, S. Salot, M. Bonneville, and E. 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