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Blood, 11 June 2009, Vol. 113, No. 24, pp. 6069-6076. Prepublished online as a Blood First Edition Paper on April 20, 2009; DOI 10.1182/blood-2009-01-199679. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-01-199679v1 113/24/6069    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 Google Scholar Articles by Dunleavy, K. Articles by Wilson, W. H. PubMed PubMed Citation Articles by Dunleavy, K. Articles by Wilson, W. H. Related Collections Free Research Articles Lymphoid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma Kieron Dunleavy1, Stefania Pittaluga1, Myron S. Czuczman2, Sandeep S. Dave1, George Wright1, Nicole Grant1, Margaret Shovlin1, Elaine S. Jaffe1, John E. Janik1, Louis M. Staudt*,1, and Wyndham H. Wilson*,1 1 Center for Cancer Research, National Cancer Institute, Bethesda, MD; and 2 Roswell Park Cancer Institute, Buffalo, NY Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed distinct molecular subtypes that include germinal center B cell–like (GCB) and activated B cell–like (ABC) DLBCL. ABC DLBCL has a worse survival after upfront chemotherapy and is characterized by constitutive activation of the antiapoptotic nuclear factor–kappa B (NF-B) pathway, which can inhibit chemotherapy. We hypothesized that inhibition of NF-B might sensitize ABC but not GCB DLBCL to chemotherapy and improve outcome. As the proteasome inhibitor bortezomib can inhibit NF-B through blocking IB degradation, we investigated bortezomib alone followed by bortezomib and doxorubicin-based chemotherapy in recurrent DLBCL. Tumor tissue was analyzed by gene expression profiling and/or immunohistochemistry to identify molecular DLBCL subtypes. As a control, we showed that relapsed/refractory ABC and GCB DLBCL have equally poor survivals after upfront chemotherapy. Bortezomib alone had no activity in DLBCL, but when combined with chemotherapy, it demonstrated a significantly higher response (83% vs 13%; P < .001) and median overall survival (10.8 vs 3.4 months; P = .003) in ABC compared with GCB DLBCL, respectively. These results suggest bortezomib enhances the activity of chemotherapy in ABC but not GCB DLBCL, and provide a rational therapeutic approach based on genetically distinct DLBCL subtypes. This trial is registered with http://www.ClinicalTrials.gov under identifier NCT00057902 [ClinicalTrials.gov] . CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Aster and J. Kutok Complexity Made Simple in Diffuse Large B-Cell Lymphoma Clin. Cancer Res., September 1, 2009; 15(17): 5291 - 5293. [Abstract] [Full Text] [PDF]

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