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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5068-5077. Prepublished online as a Blood First Edition Paper on March 11, 2008; DOI 10.1182/blood-2007-09-115170. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-09-115170v1 111/10/5068    most recent 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 Leleu, X. Articles by Ghobrial, I. M. Search for Related Content PubMed PubMed Citation Articles by Leleu, X. Articles by Ghobrial, I. M. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Targeting NF-B in Waldenstrom macroglobulinemia Xavier Leleu1,2,*, Jérôme Eeckhoute1,*, Xiaoying Jia1, Aldo M. Roccaro1, Anne-Sophie Moreau1,2, Mena Farag1, Antonio Sacco1, Hai T. Ngo1, Judith Runnels1, Molly R. Melhem1, Nicolas Burwick1, Abdelkareem Azab1, Feda Azab1, Zachary Hunter1, Evdoxia Hatjiharissi1, Daniel R. Carrasco1, Steven P. Treon1, Thomas E. Witzig3, Teru Hideshima1, Myles Brown1, Kenneth C. Anderson1, and Irene M. Ghobrial1 1 Medical Oncology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA; 2 Service des Maladies du Sang et Laboratoire d'Immunologie, CHRU, Lille, France; and 3 Division of Hematology, Mayo Clinic, Rochester, MN The nuclear factor-B (NF-B) path-way has been implicated in tumor B-cell survival, growth, and resistance to therapy. Because tumor cells overcome single-agent antitumor activity, we hypothesized that combination of agents that target differentially NF-B pathway will induce significant cytotoxicity. Therapeutic agents that target proteasome and Akt pathways should induce significant activity in B-cell malignancies as both pathways impact NF-B activity. We demonstrated that perifosine and bortezomib both targeted NF-B through its recruitment to the promoter of its target gene IB using chromatin immunoprecipitation assay. This combination led to synergistic cytotoxicity in Waldenstrom macroglobulinemia (WM) cells that was mediated through a combined reduction of the PI3K/Akt and ERK signaling pathways, found to be critical for survival of WM cells. Moreover, a combination of these drugs with the CD20 monoclonal antibody rituximab further increased their cytotoxic activity. Thus, effective WM therapy may require combination regimens targeting the NF-B pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. T. Ngo, A. K. Azab, M. Farag, X. Jia, M. M. Melhem, J. Runnels, A. M. Roccaro, F. Azab, A. Sacco, X. Leleu, et al. Src Tyrosine Kinase Regulates Adhesion and Chemotaxis in Waldenstrom Macroglobulinemia Clin. Cancer Res., October 1, 2009; 15(19): 6035 - 6041. [Abstract] [Full Text] [PDF] S. P. Treon, L. Ioakimidis, J. D. Soumerai, C. J. Patterson, P. Sheehy, M. Nelson, M. Willen, J. Matous, J. Mattern II, J. G. Diener, et al. Primary Therapy of Waldenstrom Macroglobulinemia With Bortezomib, Dexamethasone, and Rituximab: WMCTG Clinical Trial 05-180 J. Clin. Oncol., August 10, 2009; 27(23): 3830 - 3835. [Abstract] [Full Text] [PDF] A. M. Roccaro, A. Sacco, B. Thompson, X. Leleu, A. K. Azab, F. Azab, J. Runnels, X. Jia, H. T. Ngo, M. R. Melhem, et al. MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma Blood, June 25, 2009; 113(26): 6669 - 6680. [Abstract] [Full Text] [PDF] A. Vacca and F. Dammacco MicroRNAs to know in Waldenstrom macroglobulinemia Blood, April 30, 2009; 113(18): 4133 - 4134. [Full Text] [PDF] A. M. Roccaro, A. Sacco, C. Chen, J. Runnels, X. Leleu, F. Azab, A. K. Azab, X. Jia, H. T. Ngo, M. R. Melhem, et al. microRNA expression in the biology, prognosis, and therapy of Waldenstrom macroglobulinemia Blood, April 30, 2009; 113(18): 4391 - 4402. [Abstract] [Full Text] [PDF] E. Braggio, J. J. Keats, X. Leleu, S. Van Wier, V. H. Jimenez-Zepeda, R. Valdez, R. F.J. Schop, T. Price-Troska, K. Henderson, A. Sacco, et al. Identification of Copy Number Abnormalities and Inactivating Mutations in Two Negative Regulators of Nuclear Factor-{kappa}B Signaling Pathways in Waldenstrom's Macroglobulinemia Cancer Res., April 15, 2009; 69(8): 3579 - 3588. [Abstract] [Full Text] [PDF] P. L. Tazzari, G. Tabellini, F. Ricci, V. Papa, R. Bortul, F. Chiarini, C. Evangelisti, G. Martinelli, A. Bontadini, L. Cocco, et al. Synergistic Proapoptotic Activity of Recombinant TRAIL Plus the Akt Inhibitor Perifosine in Acute Myelogenous Leukemia Cells Cancer Res., November 15, 2008; 68(22): 9394 - 9403. [Abstract] [Full Text] [PDF] P. L. Bergsagel and W. M. Kuehl WSU-WM and BCWM.1 should not be assumed to represent Waldenstrom macroglobulinemia cell lines Blood, August 1, 2008; 112(3): 917 - 917. [Full Text] [PDF]

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