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Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2002, Vol. 99, No. 9, pp. 3398-3403 NEOPLASIA Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma Franziska Jundt, Ioannis Anagnostopoulos, Reinhold Förster, Stephan Mathas, Harald Stein, and Bernd Dörken From Charité, Robert-Rössle-Klinik, Humboldt University of Berlin; Max Delbrück Center for Molecular Medicine, Berlin; Institute of Pathology, Klinikum Benjamin Franklin, Free University of Berlin; Section of Experimental Surgery and Immunology, Clinic for Surgery, University of Erlangen-Nürnberg, Germany. Notch signaling controls cell fate decisions of hematopoietic progenitors by inhibiting certain steps of differentiation and inducing either self-renewal or differentiation toward lymphoid or myeloid lineages. In addition, truncated Notch1 alleles could be associated with 10% of all cases of human T lymphoblastic leukemia and, when introduced into mouse bone marrow stem cells, cause T-cell neoplasms. However, functional links between the abundant expression of intact Notch1 and oncogenesis are still lacking. Here we show that Notch1 is highly expressed in B- and T-cell-derived tumor cells of Hodgkin and anaplastic large cell lymphoma. We demonstrate a novel mechanism for the oncogenic capacity of Notch1 by showing that the interaction between intact Notch1 on tumor cells and its ligand Jagged1 dramatically induces proliferation and inhibition of apoptosis in vitro. We further provide evidence that in Hodgkin and anaplastic large cell lymphoma, Jagged1 is expressed in malignant and in bystander cells colocalizing with Notch1-positive tumor cells. Notch1 signaling may therefore be activated in tumor cells by Jagged1 through homotypic or heterotypic cell-cell interactions, and it seems likely that these interactions contribute to lymphomagenesis in vivo. Thus, our data suggest that activated Notch1 signaling plays an important role in the pathobiology of Hodgkin and anaplastic large cell lymphoma and that it might be a potential new target for treatment. © 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: C. C. Pinnix, J. T. Lee, Z.-J. Liu, R. McDaid, K. Balint, L. J. Beverly, P. A. Brafford, M. Xiao, B. Himes, S. E. Zabierowski, et al. Active Notch1 Confers a Transformed Phenotype to Primary Human Melanocytes Cancer Res., July 1, 2009; 69(13): 5312 - 5320. [Abstract] [Full Text] [PDF] H. Kohlhof, F. Hampel, R. Hoffmann, H. Burtscher, U. H. Weidle, M. Holzel, D. Eick, U. Zimber-Strobl, and L. J. 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Pear Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies Blood, December 1, 2005; 106(12): 3898 - 3906. [Abstract] [Full Text] [PDF] T. Stuhmer, M. Chatterjee, M. Hildebrandt, P. Herrmann, H. Gollasch, C. Gerecke, S. Theurich, L. Cigliano, R. A. Manz, P. T. Daniel, et al. Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple myeloma Blood, November 15, 2005; 106(10): 3609 - 3617. [Abstract] [Full Text] [PDF] D. Re, R. Kuppers, and V. Diehl Molecular Pathogenesis of Hodgkin's Lymphoma J. Clin. Oncol., September 10, 2005; 23(26): 6379 - 6386. [Abstract] [Full Text] [PDF] I. C. Cuevas, A. L. Slocum, P. Jun, J. F. Costello, A. W. Bollen, G. J. Riggins, M. W. McDermott, and A. Lal Meningioma Transcript Profiles Reveal Deregulated Notch Signaling Pathway Cancer Res., June 15, 2005; 65(12): 5070 - 5075. [Abstract] [Full Text] [PDF] C. Atayar, S. Poppema, T. Blokzijl, G. Harms, M. 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