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This Article Full Text Full Text (PDF) 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 Hubmann, R. Articles by Berger, R. Search for Related Content PubMed PubMed Citation Articles by Hubmann, R. Articles by Berger, R. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2002, Vol. 99, No. 10, pp. 3742-3747 NEOPLASIA Notch2 is involved in the overexpression of CD23 in B-cell chronic lymphocytic leukemia Rainer Hubmann, Josef D. Schwarzmeier, Medhat Shehata, Martin Hilgarth, Markus Duechler, Markus Dettke, and Rudolf Berger From the Department of Hematology, Clinic of Internal Medicine I, the Department of Blood Group Serology and Transfusion Medicine, and the Ludwig Boltzmann-Institute for Cytokine Research, University of Vienna, Vienna, Austria. Members of the Notch family encode transmembrane receptors that modulate differentiation, proliferation, and apoptotic programs of many precursor cells, including hematopoietic progenitors. Stimulation of Notch causes cleavage followed by translocation of the intracellular domain (NotchIC) to the nucleus, where it activates transcription of CBF1 responsive genes. The aim of this study was to elucidate the mechanisms leading to the overexpression of CD23, a striking feature of B-cell chronic lymphocytic leukemia (B-CLL) cells. By electrophoretic mobility shift assays, we identified a transcription factor complex (C1) that binds sequence specific to one known and 4 newly identified putative CBF1 recognition sites in the CD23a core promoter region. With the use of Epstein-Barr virus (EBV)-infected B cells as a model for CBF1 mediated CD23a expression, C1 was found to be EBV inducible. Supershift assays revealed that the nuclear form of Notch2 is a component of C1 in B-CLL cells, supporting a model in which NotchIC activates transcription by binding to CBF1 tethered to DNA. Transient transfection of REH pre-B cells with an activated form of Notch2 induced endogenous CD23a, confirming that CD23a is a target gene of Notch2 signaling. Finally, reverse transcription-polymerase chain reaction and kinetic analysis demonstrated that the Notch2 oncogene is not only overexpressed in B-CLL cells but might also be related to the failure of apoptosis characteristic for this disease. In conclusion, these data suggest that deregulation of Notch2 signaling is involved in the aberrant expression of CD23 in B-CLL. © 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: H. Kohlhof, F. Hampel, R. Hoffmann, H. Burtscher, U. H. Weidle, M. Holzel, D. Eick, U. Zimber-Strobl, and L. J. Strobl Notch1, Notch2, and Epstein-Barr virus-encoded nuclear antigen 2 signaling differentially affects proliferation and survival of Epstein-Barr virus-infected B cells Blood, May 28, 2009; 113(22): 5506 - 5515. [Abstract] [Full Text] [PDF] P. Secchiero, E. Melloni, M. G. di Iasio, M. Tiribelli, E. Rimondi, F. Corallini, V. Gattei, and G. Zauli Nutlin-3 up-regulates the expression of Notch1 in both myeloid and lymphoid leukemic cells, as part of a negative feedback antiapoptotic mechanism Blood, April 30, 2009; 113(18): 4300 - 4308. [Abstract] [Full Text] [PDF] E. Rosati, R. Sabatini, G. Rampino, A. Tabilio, M. Di Ianni, K. Fettucciari, A. Bartoli, S. Coaccioli, I. Screpanti, and P. Marconi Constitutively activated Notch signaling is involved in survival and apoptosis resistance of B-CLL cells Blood, January 22, 2009; 113(4): 856 - 865. [Abstract] [Full Text] [PDF] B. Sivasankaran, M. Degen, A. Ghaffari, M. E. Hegi, M.-F. Hamou, M.-C. S. Ionescu, C. Zweifel, M. Tolnay, M. Wasner, S. Mergenthaler, et al. Tenascin-C Is a Novel RBPJ{kappa}-Induced Target Gene for Notch Signaling in Gliomas Cancer Res., January 15, 2009; 69(2): 458 - 465. [Abstract] [Full Text] [PDF] Y. Nefedova, D. M. Sullivan, S. C. Bolick, W. S. Dalton, and D. I. Gabrilovich Inhibition of Notch signaling induces apoptosis of myeloma cells and enhances sensitivity to chemotherapy Blood, February 15, 2008; 111(4): 2220 - 2229. [Abstract] [Full Text] [PDF] V. Bolos, J. Grego-Bessa, and J. L. de la Pompa Notch Signaling in Development and Cancer Endocr. 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	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020