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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3511-3515.
Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-07-2254.


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NEOPLASIA

Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells

Franziska Jundt, Kristina Schulze Pröbsting, Ioannis Anagnostopoulos, Gwendolin Muehlinghaus, Manik Chatterjee, Stephan Mathas, Ralf C. Bargou, Rudolf Manz, Harald Stein, and Bernd Dörken

From the Department of Hematology and Oncology, Charité, Campus Virchow-Klinikum, University Medicine Berlin, Berlin, Germany; Max Delbrück Center for Molecular Medicine, Berlin, Germany; Institute of Pathology, Charité, Campus Benjamin Franklin, University Medicine Berlin, Berlin, Germany; and Deutsches Rheumaforschungszentrum, Berlin, Germany.

Notch receptors expressed on hematopoietic stem cells interact with their ligands on bone marrow stromal cells and thereby control cell fate decisions and survival. We recently demonstrated that Notch signaling is involved in proliferation and survival of B cell-derived tumor cells of classic Hodgkin disease and described a novel mechanism for the oncogenic capacity of Notch. In this study we investigated whether Notch signaling is involved in the tight interactions between neoplastic plasma cells and their bone marrow microenvironment, which are essential for tumor cell growth in multiple myeloma (MM). Here we demonstrate that Notch receptors and their ligand Jagged1 are highly expressed in cultured and primary MM cells, whereas nonneoplastic counterparts show low to undetectable levels of Notch. Functional data indicate that ligand-induced Notch signaling is a growth factor for MM cells and suggest that these interactions contribute to myelomagenesis in vivo. (Blood. 2004;103:3511-3515)


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