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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2927-2934. Prepublished online as a Blood First Edition Paper on July 15, 2008; DOI 10.1182/blood-2008-02-137513. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-02-137513v1 112/7/2927    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kuo, S.-H. Articles by Cheng, A.-L. Search for Related Content PubMed PubMed Citation Articles by Kuo, S.-H. Articles by Cheng, A.-L. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Overexpression of B cell–activating factor of TNF family (BAFF) is associated with Helicobacter pylori–independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma Sung-Hsin Kuo14, Pei-Yen Yeh1,3, Li-Tzong Chen57, Ming-Shiang Wu2, Chung-Wu Lin8, Kun-Huei Yeh1,3, Yi-Shin Tzeng1,3, Jing-Yi Chen1,3, Ping-Ning Hsu2, Jaw-Town Lin2, and Ann-Lii Cheng13,5 Departments of1 Oncology and 2 Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei; 3 Cancer Research Center, National Taiwan University College of Medicine, Taipei; 4 Department of Oncology, National Taiwan University Hospital, Yun-Lin Branch, Yunlin; 5 National Institute of Cancer Research, National Health Research Institutes, Tainan; 6 Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung; 7 Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan; and 8 Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan We have recently demonstrated that nuclear expression of BCL10 predicts Helicobacter pylori (HP) independence of early-stage gastric diffuse large B-cell lymphoma (DLBCL) with histologic evidence of mucosa-associated lymphoid tissue (MALT). In this study, we examined the role of B cell–activating factor of TNF family (BAFF) in mediating BCL10 nuclear translocation and HP independence of gastric DLBCL (MALT). We used immunohistochemistry and immunoblotting to measure the expression of BAFF, pAKT, BCL3, BCL10, and NF-B. Transactivity of NF-B was measured by electromobility shift assay. In lymphoma samples from 26 patients with gastric DLBCL (MALT), we detected aberrant expression of BAFF in 7 of 10 (70%) HP-independent and in 3 of 16 (18.8%) HP-dependent cases (P = .015). BAFF overexpression was associated with pAKT expression (P = .032), and nuclear expression of BCL3 (P = .014), BCL10 (P = .015), and NF-B (P = .004). In B-cell lymphoma Pfeiffer cells, BAFF activated NF-B and AKT; the activated NF-B up-regulated BCL10, and the activated AKT caused formation of BCL10/BCL3 complexes that translocated to the nucleus. Inhibition of AKT by LY294002 (a PI3K inhibitor) blocked BCL10 nuclear translocation, NF-B transactivity, and BAFF expression. Our results indicate that autocrine BAFF signal transduction pathways may contribute to HP-independent growth of gastric DLBCL (MALT). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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