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Blood, 15 January 2007, Vol. 109, No. 2, pp. 703-710. Prepublished online as a Blood First Edition Paper on September 14, 2006; DOI 10.1182/blood-2006-06-027755. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-06-027755v1 109/2/703    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 Endo, T. Articles by Kipps, T. J. Search for Related Content PubMed PubMed Citation Articles by Endo, T. Articles by Kipps, T. J. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA BAFF and APRIL support chronic lymphocytic leukemia B-cell survival through activation of the canonical NF-B pathway Tomoyuki Endo1, Mitsufumi Nishio1, Thomas Enzler2, Howard B. Cottam1, Tetsuya Fukuda1, Danelle F. James1, Michael Karin2, and Thomas J. Kipps1, 1 Moores Cancer Center and 2 Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California at San Diego, La Jolla, CA Chronic lymphocytic leukemia (CLL) B cells express BR3, the specific receptor for the B cell–activating factor of tumor necrosis factor family (BAFF). CLL cells also express 2 other receptors for BAFF, namely B-cell maturation antigen (BCMA) and the transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI), which also bind a proliferation-inducing ligand (APRIL). We found that signaling through BR3, but not BCMA or TACI, activated the alternative nuclear factor of B (NF-B) pathway in CLL cells, whereas signaling through BCMA/TACI induced activation of the canonical NF-B pathway. Blocking BR3 did not inhibit the capacity of BAFF to support CLL cell survival in vitro. On the other hand, specifically blocking the canonical NF-B pathway with UTC, an inhibitor of IB kinase ß (IKKß), or transfection of CLL cells with the IB super-repressor, blocked the capacity of BAFF and APRIL to promote CLL cell survival in vitro. This contrasts what is found with normal blood B cells, which apparently depend on activation of the alternative NF-B pathway for BAFF-enhanced survival. These findings suggest that inhibitors of protein kinase IKKß, which is required for activation of the canonical NF-B pathway, might have a therapeutic role in this disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Hewamana, S. Alghazal, T. T. Lin, M. Clement, C. Jenkins, M. L. Guzman, C. T. Jordan, S. Neelakantan, P. A. Crooks, A. K. Burnett, et al. The NF-{kappa}B subunit Rel A is associated with in vitro survival and clinical disease progression in chronic lymphocytic leukemia and represents a promising therapeutic target Blood, May 1, 2008; 111(9): 4681 - 4689. [Abstract] [Full Text] [PDF] S.-W. Kim, D. W. Oleksyn, R. M. Rossi, C. T. Jordan, I. Sanz, L. Chen, and J. Zhao Protein kinase C-associated kinase is required for NF-{kappa}B signaling and survival in diffuse large B-cell lymphoma cells Blood, February 1, 2008; 111(3): 1644 - 1653. [Abstract] [Full Text] [PDF] Y. Dai, S. Chen, L. B. Kramer, V. L. Funk, P. Dent, and S. Grant Interactions between Bortezomib and Romidepsin and Belinostat in Chronic Lymphocytic Leukemia Cells Clin. Cancer Res., January 15, 2008; 14(2): 549 - 558. [Abstract] [Full Text] [PDF] W. Y. Lin, Q. Gong, D. Seshasayee, Z. Lin, Q. Ou, S. Ye, E. Suto, J. Shu, W. Pun Lee, C.-W. V. Lee, et al. Anti-BR3 antibodies: a new class of B-cell immunotherapy combining cellular depletion and survival blockade Blood, December 1, 2007; 110(12): 3959 - 3967. [Abstract] [Full Text] [PDF] M. Romagnoli, G. Desplanques, S. Maiga, S. Legouill, M. Dreano, R. Bataille, and S. Barille-Nion Canonical Nuclear Factor {kappa}B Pathway Inhibition Blocks Myeloma Cell Growth and Induces Apoptosis in Strong Synergy with TRAIL Clin. Cancer Res., October 15, 2007; 13(20): 6010 - 6018. [Abstract] [Full Text] [PDF] I. Binsky, M. Haran, D. Starlets, Y. Gore, F. Lantner, N. Harpaz, L. Leng, D. M. Goldenberg, L. Shvidel, A. Berrebi, et al. IL-8 secreted in a macrophage migration-inhibitory factor- and CD74-dependent manner regulates B cell chronic lymphocytic leukemia survival PNAS, August 14, 2007; 104(33): 13408 - 13413. [Abstract] [Full Text] [PDF]

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