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Blood, 15 January 2007, Vol. 109, No. 2, pp. 729-739. Prepublished online as a Blood First Edition Paper on September 7, 2006; DOI 10.1182/blood-2006-04-015958. This Article Full Text (PDF) All Versions of this Article: blood-2006-04-015958v1 109/2/729    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chiu, A. Articles by Cerutti, A. Search for Related Content PubMed PubMed Citation Articles by Chiu, A. Articles by Cerutti, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 10, 2006 Accepted August 21, 2006 Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL April Chiu, Weifeng Xu, Bing He, Stacey R. Dillon, Jane A. Gross, Eric Sievers, Xugang Qiao, Paul Santini, Elizabeth Hyjek, Joong-won Lee, Ethel Cesarman, Amy Chadburn, Daniel M Knowles, and Andrea Cerutti* Dept. of Pathology & Laboratory Medicine of Weill Medical College of Cornell University, New York,NY ZymoGenetics, Inc., Seattle, WA USA * Corresponding author; email: acerutti{at}med.cornell.edu. Hodgkin lymphoma (HL) originates from the clonal expansion of malignant Hodgkin and Reed Sternberg (HRS) cells. These B cell-derived elements constitute less than 10% of the tumoral mass. The remaining tissue is comprised of an inflammatory infiltrate that includes myeloid cells. Myeloid cells activate B cells by producing BAFF and APRIL, which engage TACI, BCMA and BAFF-R receptors on the B cells. Here we studied the role of BAFF and APRIL in HL. Inflammatory and HRS cells from HL tumors expressed BAFF and APRIL. Unlike their putative germinal center B cell precursors, HRS cells lacked BAFF-R, but expressed TACI and BCMA, a phenotype similar to that of plasmacytoid B cells. BAFF and APRIL enhanced HRS cell survival and proliferation by delivering non-redundant signals via TACI and BCMA receptors through both autocrine and paracrine pathways. These signals caused NF-B activation, Bcl-2, Bcl-xL and c-Myc up-regulation, and Bax down-regulation and were amplified by APRIL-binding proteoglycans on HRS cells. Interruption of BAFF and APRIL signaling by TACI-Ig decoy receptor, which binds to and neutralizes BAFF and APRIL, or small interfering RNAs targeting BAFF, APRIL, TACI and BCMA inhibited HRS cell accumulation in vitro and might attenuate HL expansion in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020