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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1392-1399. Prepublished online as a Blood First Edition Paper on May 3, 2005; DOI 10.1182/blood-2004-12-4901. This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2004-12-4901v1 106/4/1392    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 Feuerhake, F. Articles by Shipp, M. A. Search for Related Content PubMed PubMed Citation Articles by Feuerhake, F. Articles by Shipp, M. A. Related Collections Neoplasia Gene Expression Genomics Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA NFB activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes Friedrich Feuerhake, Jeffery L. Kutok, Stefano Monti, Wen Chen, Ann S. LaCasce, Giorgio Cattoretti, Paul Kurtin, Geraldine S. Pinkus, Laurence de Leval, Nancy L. Harris, Kerry J. Savage, Donna Neuberg, Thomas M. Habermann, Riccardo Dalla-Favera, Todd R. Golub, Jon C. Aster, and Margaret A. Shipp From the Department of Medical Oncology, the Department of Biostatistics, and the Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA; the Department of Pathology, Brigham and Women's Hospital, Boston, MA; The Broad Institute, Cambridge, MA; the Institute for Cancer Genetics, Columbia University, New York, NY; the Department of Pathology and the Division of Hematology and Department of Medicine, Mayo Clinic, Rochester, MN; the Department of Pathology, Massachusetts General Hospital, Boston, MA; and the Howard Hughes Medical Institute, Boston, MA. Primary mediastinal large B-cell lymphoma (MLBCL) shares important clinical and molecular features with classic Hodgkin lymphoma, including nuclear localization of the nuclear factor B (NFB) subunit c-REL (reticuloendotheliosis viral oncogene homolog) in a pilot series. Herein, we analyzed c-REL subcellular localization in additional primary MLBCLs and characterized NFB activity and function in a MLBCL cell line. The new primary MLBCLs had prominent c-REL nuclear staining, and the MLBCL cell line exhibited high levels of NFB binding activity. MLBCL cells expressing a superrepressor form of inhibitor of kappa B alpha signaling (IB) had a markedly higher rate of apoptosis, implicating constitutive NFB activity in MLBCL cell survival. The transcriptional profiles of newly diagnosed primary MLBCLs and diffuse large B-cell lymphomas (DLBCLs) were then used to characterize the NFB target gene signatures of MLBCL and specific DLBCL subtypes. MLBCLs expressed increased levels of NFB targets that promote cell survival and favor antiapoptotic tumor necrosis factor (TNF) signaling. In contrast, activated B cell (ABC)-like DLBCLs had a more restricted, potentially developmentally regulated, NFB target gene signature. Of interest, the newly characterized host response DLBCL subtype had a robust NFB target gene signature that partially overlapped that of primary MLBCL. In this large series of primary MLBCLs and DLBCLs, NFB activation was not associated with amplification of the cREL locus, suggesting alternative pathogenetic mechanisms. (Blood. 2005;106:1392-1399) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. J. Rodig, J. Ouyang, P. Juszczynski, T. Currie, K. Law, D. S. Neuberg, G. A. Rabinovich, M. A. Shipp, and J. L. Kutok AP1-Dependent Galectin-1 Expression Delineates Classical Hodgkin and Anaplastic Large Cell Lymphomas from Other Lymphoid Malignancies with Shared Molecular Features Clin. Cancer Res., June 1, 2008; 14(11): 3338 - 3344. [Abstract] [Full Text] [PDF] N. Gupta, J. Delrow, A. Drawid, A. M. Sengupta, G. Fan, and C. Gelinas Repression of B-Cell Linker (BLNK) and B-Cell Adaptor for Phosphoinositide 3-Kinase (BCAP) Is Important for Lymphocyte Transformation by Rel Proteins Cancer Res., February 1, 2008; 68(3): 808 - 814. 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Shipp Molecular Signatures Define New Rational Treatment Targets in Large B-Cell Lymphomas Hematology, January 1, 2007; 2007(1): 265 - 269. [Abstract] [Full Text] [PDF] H. Takahashi, F. Feuerhake, J. L. Kutok, S. Monti, P. Dal Cin, D. Neuberg, J. C. Aster, and M. A. Shipp FAS Death Domain Deletions and Cellular FADD-like Interleukin 1{beta} Converting Enzyme Inhibitory Protein (Long) Overexpression: Alternative Mechanisms for Deregulating the Extrinsic Apoptotic Pathway in Diffuse Large B-Cell Lymphoma Subtypes. Clin. Cancer Res., June 1, 2006; 12(11): 3265 - 3271. [Abstract] [Full Text] [PDF] K. J. Savage Primary mediastinal large B-cell lymphoma. Oncologist, May 1, 2006; 11(5): 488 - 495. [Abstract] [Full Text] [PDF] H. Takahashi, F. Feuerhake, S. Monti, J. L. Kutok, J. C. Aster, and M. A. Shipp Lack of IKBA coding region mutations in primary mediastinal large B-cell lymphoma and the host response subtype of diffuse large B-cell lymphoma Blood, January 15, 2006; 107(2): 844 - 845. 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