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Blood, 1 August 2005, Vol. 106, No. 3, pp. 1012-1020. Prepublished online as a Blood First Edition Paper on April 28, 2005; DOI 10.1182/blood-2004-03-0889. This Article Full Text (PDF) All Versions of this Article: 2004-03-0889v1 106/3/1012    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 Nishio, M. Articles by Kipps, T. J Search for Related Content PubMed PubMed Citation Articles by Nishio, M. Articles by Kipps, T. J Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 9, 2004 Accepted March 28, 2005 Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1 Mitsufumi Nishio, Tomoyuki Endo, Nobuhiro Tsukada, Junko Ohata, Shinichi Kitada, John C Reed, Nathan J Zvaifler, and Thomas J Kipps* Department of Medicine, University of California, San Diego, La Jolla, CA, USA The Burnham Institute, La Jolla, CA, USA * Corresponding author; email: tkipps{at}ucsd.edu. We examined expression of B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) on chronic lymphocytic leukemia (CLL) B cells and nurselike cells (NLC), which differentiate from CD14+ cells when cultured with CLL B cells. NLC expressed significantly higher levels of APRIL than monocytes and significantly higher levels of BAFF and APRIL than CLL B cells. Also, the viability of CLL B cells cultured with NLC was significantly reduced when CLL B cells were cultured with decoy receptor of B-cell maturation antigen (BCMA), which can bind both BAFF and APRIL, but not with BAFF-R:Fc, which only binds to BAFF. The effect(s) of BAFF or APRIL on leukemia cell survival appeared additive and distinct from that of stromal cell-derived factor-1 alpha (SDF-1), which in contrast to BAFF or APRIL induced leukemia-cell phosphorylation of p44/42 mitogen-activated protein-kinase (ERK 1/2) and AKT. Conversely, BAFF and APRIL, but not SDF-1, induced CLL-cell activation of the NF-B1, and enhanced CLL-cell expression of the anti-apoptotic protein Mcl-1. However, BAFF, but not APRIL, also induced CLL-cell activation of NF-B2. We conclude that BAFF and APRIL from NLC can function in a paracrine manner to support leukemia cell survival via mechanisms that are distinct from those of SDF-1, indicating that NLC use multiple distinct pathways to support CLL-cell survival. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: APRIL showers cause CLL and myeloma to flower John Shaughnessy, Jr Blood 2005 106: 766-767. [Full Text] [PDF] This article has been cited by other articles: T. Enzler, A. P. Kater, W. Zhang, G. F. Widhopf II, H.-Y. Chuang, J. Lee, E. Avery, C. M. Croce, M. Karin, and T. J. Kipps Chronic lymphocytic leukemia of E{micro}-TCL1 transgenic mice undergoes rapid cell turnover that can be offset by extrinsic CD257 to accelerate disease progression Blood, November 12, 2009; 114(20): 4469 - 4476. [Abstract] [Full Text] [PDF] A. V. Kurtova, K. Balakrishnan, R. Chen, W. Ding, S. Schnabl, M. P. Quiroga, M. Sivina, W. G. Wierda, Z. Estrov, M. 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