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Blood, 1 January 2004, Vol. 103, No. 1, pp. 242-251. Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-04-1048. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 2003-04-1048v1 103/1/242    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 Brocke-Heidrich, K. Articles by Horn, F. Search for Related Content PubMed PubMed Citation Articles by Brocke-Heidrich, K. Articles by Horn, F. Related Collections Neoplasia Apoptosis Oncogenes and Tumor Suppressors Signal Transduction Gene Expression Genomics Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Interleukin-6–dependent gene expression profiles in multiple myeloma INA-6 cells reveal a Bcl-2 family–independent survival pathway closely associated with Stat3 activation Katja Brocke-Heidrich, Antje K. Kretzschmar, Gabriele Pfeifer, Christian Henze, Dennis Löffler, Dirk Koczan, Hans-Jürgen Thiesen, Renate Burger, Martin Gramatzki, and Friedemann Horn From the Institute of Clinical Immunology and Transfusion Medicine, University of Leipzig, Leipzig, Germany; Department of Immunology, University of Rostock, Faculty of Medicine, Rostock, Germany; Division of Hematology/Oncology, Department of Medicine III, University of Erlangen-Nürnberg, Erlangen, Germany. Interleukin 6 (IL-6) is a growth and survival factor for multiple myeloma cells. As we report here, the IL-6–dependent human myeloma cell line INA-6 responds with a remarkably rapid and complete apoptosis to cytokine withdrawal. Among the antiapoptotic members of the B-cell lymphoma-2 (Bcl-2) family of apoptosis regulators, only myeloid cell factor-1 (Mcl-1) was slightly induced by IL-6. Overexpression studies demonstrated, however, that IL-6 does not exert its survival effect primarily through this pathway. The IL-6 signal transduction pathways required for survival and the target genes controlled by them were analyzed by using mutated receptor chimeras. The activation of signal transducer and activator of transcription 3 (Stat3) turned out to be obligatory for the survival of INA-6 cells. The same held true for survival and growth of XG-1 myeloma cells. Gene expression profiling of INA-6 cells by using oligonucleotide microarrays revealed many novel IL-6 target genes, among them several genes coding for transcriptional regulators involved in B-lymphocyte differentiation as well as for growth factors and receptors potentially implicated in autocrine or paracrine growth control. Regulation of most IL-6 target genes required the activation of Stat3, underscoring its central role for IL-6 signal transduction. Taken together, our data provide evidence for the existence of an as yet unknown Stat3-dependent survival pathway in myeloma cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. H. Shain, D. N. Yarde, M. B. Meads, M. Huang, R. Jove, L. A. Hazlehurst, and W. S. 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