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Blood, 15 April 2004, Vol. 103, No. 8, pp. 3175-3184. Prepublished online as a Blood First Edition Paper on December 18, 2003; DOI 10.1182/blood-2003-06-2151. This Article Full Text (PDF) All Versions of this Article: 2003-06-2151v1 103/8/3175    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 Bharti, A. C Articles by Aggarwal, B. B Search for Related Content PubMed PubMed Citation Articles by Bharti, A. C Articles by Aggarwal, B. B Social Bookmarking                   What's this? Submitted July 8, 2003 Accepted December 3, 2003 Nuclear factor-B and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and their suppression leads to apoptosis Alok C Bharti, Shishir Shishodia, James M Reuben, Donna Weber, Raymond Alexanian, Saroj Raj-Vadhan, Zeev Estrov, Moshe Talpaz, and Bharat B Aggarwal* Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA Department of Lymphoma and Myeloma, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA * Corresponding author; email: aggarwal{at}mdanderson.org. Chemoresistance is a major problem in the treatment of patients with multiple myeloma (MM). Because of the central role of the nuclear transcription factors NF-B and STAT3 in chemoresistance, cell survival and proliferation, we investigated whether MM cells derived from patients express activated NF-B and STAT3 and if their suppression induces apoptosis. We assayed CD138+ cells from the bone marrow of 22 MM patients and checked for the activated forms of NF-B and STAT3 by immunocytochemistry. We found that MM cells from all the patients expressed the activated forms of NF-B and STAT3, but to a variable degree (NF-B: low-3/22; moderate-5/22; or high 14/22; STAT3: none 1/22; low-3/22; moderate-5/22; or high 14/22). Constitutive activation of NF-B was in some cases also independently confirmed by electrophoretic mobility gel shift assay. In contrast to MM patients, activated form of NF-B and STAT3 were absent in cells from healthy individuals. Suppression of NF-B and STAT3 activation in MM cells by ex vivo treatment with curcumin (diferuloylmethane) resulted in a decrease in adhesion to bone marrow stromal cells, cytokine secretion and in the viability of cells. When compared to curcumin, dexamethasone was less effective in suppression of NF-B activation and induction of apoptosis in myeloma cells. Overall, our results indicate that fresh cells from MM patients express constitutively active NF-B and STAT3, and suppression of these transcription factors inhibits the survival of the cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. V. Rajkumar Prevention of Progression in Monoclonal Gammopathy of Undetermined Significance Clin. Cancer Res., September 15, 2009; 15(18): 5606 - 5608. [Abstract] [Full Text] [PDF] S. Wang, G. Tricot, L. Shi, W. Xiong, Z. Zeng, H. Xu, M. Zangari, B. Barlogie, J. D. Shaughnessy Jr, and F. 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