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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3480-3489. Prepublished online as a Blood First Edition Paper on December 4, 2003; DOI 10.1182/blood-2003-08-2970. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-08-2970v1 103/9/3480    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 Burchert, A. Articles by Neubauer, A. Search for Related Content PubMed PubMed Citation Articles by Burchert, A. Articles by Neubauer, A. Related Collections Neoplasia Apoptosis Oncogenes and Tumor Suppressors Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Interferon consensus sequence binding protein (ICSBP; IRF-8) antagonizes BCR/ABL and down-regulates bcl-2 Andreas Burchert, Dali Cai, Lorenz C. Hofbauer, Magnus K. R. Samuelsson, Emily P. Slater, Justus Duyster, Markus Ritter, Andreas Hochhaus, Rolf Müller, Martin Eilers, Manuel Schmidt, and Andreas Neubauer From the Klinikum der Philipps Universität Marburg, Klinik für Hämatologie, Onkologie und Immunologie, Marburg, Germany; Klinikum der Philipps Universität Marburg, Klinik für Gastroenterologie und Endokrinologie, Marburg, Germany; Institute of Molecular Biology and Tumor Research, Department of Medicine, Philipps University, Marburg, Germany; Department of Internal Medicine III, Laboratory of Leukemogenesis, Technical University of Munich, Munich, Germany; Fakultät für Klinische Medizin Mannheim der Universitaet Heidelberg, III, Medizinische Klinik, Mannheim, Germany; and Mologen GmbH, Berlin, Germany BCR/ABL is the causative genetic aberration in chronic myelogenous leukemia (CML). Mice lacking expression of the interferon (IFN) consensus sequence binding protein (ICSBP), an IFN-inducible transcription factor of the interferon regulatory factor (IRF) family, develop a disease similar to human CML. Mounting evidence suggests a role for ICSBP in the pathogenesis of CML. However, the underlying mechanisms are largely unknown. By stable and conditional expression of ICSBP in wild-type and BCR/ABL-transformed 32D cells (32D/wt and 32D/BA), we found that ICSBP inhibited BCR/ABL-mediated leukemogenesis in vivo. Moreover, ICSBP also overrode BCR/ABL-mediated morphology changes, chemotherapy, and imatinib resistance, as well as BCR/ABL-induced repression of differentiation. Some of these ICSBP effects may be explained in part by an ICSBP-mediated repression of bcl-2, a major antiapoptotic target of BCR/ABL, on transcriptional and protein level. Using reporter gene assays and electrophoretic mobility shift assays we identified that the bcl-2 promoter activity was inhibited by ICSBP by way of a fragment containing 2 characteristic ICSBP-responsive elements. An inverse correlation between ICSBP and bcl-2 expression was confirmed in vivo. Collectively, our findings suggest that ICSBP antagonizes BCR/ABL by down-regulation of bcl-2 and implicates a central role for ICSBP in the pathogenesis of CML, as well as a therapeutic target to overcome drug resistance in bcl-2-dependent tumors. (Blood. 2004;103:3480-3489) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Koenigsmann, C. Rudolph, S. Sander, O. Kershaw, A. D. Gruber, L. Bullinger, B. Schlegelberger, and D. Carstanjen Nf1 haploinsufficiency and Icsbp deficiency synergize in the development of leukemias Blood, May 7, 2009; 113(19): 4690 - 4701. [Abstract] [Full Text] [PDF] V. Nardi, O. 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