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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3503-3510. Prepublished online as a Blood First Edition Paper on December 11, 2003; DOI 10.1182/blood-2003-07-2340. This Article Full Text (PDF) All Versions of this Article: 2003-07-2340v1 103/9/3503    most recent Alert me when this article is cited Alert me if a correction is posted 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 Nefedova, Y. Articles by Gabrilovich, D. I Search for Related Content PubMed PubMed Citation Articles by Nefedova, Y. Articles by Gabrilovich, D. I Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted July 10, 2003 Accepted December 4, 2003 Notch-1 signaling is involved in bone marrow stroma mediated de novo drug resistance of myeloma and other malignant lymphoid cell lines Yulia Nefedova, Pingyan Cheng, Melissa Alsina, William S Dalton, and Dmitry I Gabrilovich* H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL, USA * Corresponding author; email: dgabril{at}moffitt.usf.edu. The bone marrow (BM) microenvironment plays a critical role in growth, survival, and response to chemotherapy in hematologic malignancies. However, mechanisms associated with this environmental influence remain unclear. In this study, we investigated the role of Notch family proteins in myeloma and other malignant lymphoid cell lines growth and response to chemotherapeutic drugs. All eight tested cell lines expressed Notch-3 and Notch-4, seven cell lines expressed Notch-1, and six expressed Notch-2 proteins. Interaction with BM stroma (BMS) activated Notch signaling in tumor cells. However, activation of only Notch-1, but not Notch-2, resulted in protection of tumor cells from melphalan- and mitoxantrone-induced apoptosis. This protection was associated with up-regulation of p21WAF/Cip and growth inhibition of cells. Overexpression of Notch-1 in Notch-1 negative U266 myeloma cells up-regulated p21 and resulted in protection from drug-induced apoptosis. Thus, this is a first report demonstrating that Notch-1 signaling may be a primary mechanism mediating the BMS influence on hematologic malignant cell growth and survival. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Notch signaling: a key to the pathogenesis of multiple myeloma? Laurie A. Milner Blood 2004 103: 3253-3254. [Full Text] [PDF] This article has been cited by other articles: P. Ghoshal, A. J. Nganga, J. Moran-Giuati, A. Szafranek, T. R. Johnson, A. J. Bigelow, C. M. Houde, H. Avet-Loiseau, D. J. Smiraglia, N. Ersing, et al. 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The cancer-testis antigens CT7 (MAGE-C1) and MAGE-A3/6 are commonly expressed in multiple myeloma and correlate with plasma-cell proliferation Blood, July 1, 2005; 106(1): 167 - 174. [Abstract] [Full Text] [PDF] T. Takeuchi, Y. Adachi, and Y. Ohtsuki Skeletrophin, a Novel Ubiquitin Ligase to the Intracellular Region of Jagged-2, Is Aberrantly Expressed in Multiple Myeloma Am. J. Pathol., June 1, 2005; 166(6): 1817 - 1826. [Abstract] [Full Text] [PDF] L. Yin Chondroitin Synthase 1 Is a Key Molecule in Myeloma Cell-Osteoclast Interactions J. Biol. Chem., April 22, 2005; 280(16): 15666 - 15672. [Abstract] [Full Text] [PDF] T. Matsumoto and M. Abe The Importance of Notch Signaling in Myeloma Cell-Osteoclast Interactions IBMS BoneKEy, February 1, 2005; 2(2): 7 - 10. [Full Text] [PDF] C. Houde, Y. Li, L. Song, K. Barton, Q. Zhang, J. Godwin, S. Nand, A. Toor, S. Alkan, N. V. Smadja, et al. 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