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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 30, 2004 Accepted April 20, 2005 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* Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA The Broad Institute, Cambridge, MA, USA Institute for Cancer Genetics, Columbia University, New York, NY, USA Department of Pathology, Mayo Clinic, Rochester, MN, USA Department of Pathology, Massachusetts General Hospital, Boston, MA, USA Department of Biostatistics, Dana-Farber Cancer Institute, Boston, MA, USA Division of Hematology and Department of Medicine, Mayo Clinic, Rochester, MN, USA Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Howard Hughes Medical Institute, Boston, MA, USA * Corresponding author; email: margaret_shipp{at}dfci.harvard.edu. Primary mediastinal large B-cell lymphoma (MLBCL) shares important clinical and molecular features with classical Hodgkin lymphoma, including nuclear localization of the c-REL NFB subunit in a pilot series. Herein, we analyzed c-REL subcellular location 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 super-repressor form of 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 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 anti-apoptotic TNF signaling. In contrast, "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 which partially overlapped that of primary MLBCL. In this large series of primary MLBCLs and DLBCLs, NFB activation was not associated with amplification of the c-REL locus, suggesting alternative pathogenetic mechanisms. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. A. Soucy, P. G. Smith, and M. Rolfe Targeting NEDD8-Activated Cullin-RING Ligases for the Treatment of Cancer Clin. Cancer Res., June 15, 2009; 15(12): 3912 - 3916. [Abstract] [Full Text] [PDF] G. Fan, Y. Fan, N. Gupta, I. Matsuura, F. Liu, X. Z. Zhou, K. P. Lu, and C. 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