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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3177-3188. Prepublished online as a Blood First Edition Paper on December 21, 2006; DOI 10.1182/blood-2006-09-044974. This Article Full Text (PDF) Supplemental Methods and Appendix Supplemental Tables and Figures All Versions of this Article: blood-2006-09-044974v1 109/8/3177    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 Mulligan, G. Articles by Anderson, K. C. Search for Related Content PubMed PubMed Citation Articles by Mulligan, G. Articles by Anderson, K. C. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 6, 2006 Accepted December 6, 2006 Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib George Mulligan*, Constantine Mitsiades, Barb Bryant, Fenghuang Zhan, Wee J. Chng, Steven Roels, Erik Koenig, Andrew Fergus, Yongsheng Huang, Paul Richardson, William L Trepicchio, Annemiek Broyl, Pieter Sonneveld, John D Shaughnessy Jr., P. Leif Bergsagel, David Schenkein, Dixie-Lee Esseltine, Anthony Boral, and Kenneth C. Anderson Millennium Pharmaceuticals, Inc, Cambridge, MA, United States Dana-Farber Cancer Institute, Boston, MA, United States Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, United States Mayo Clinic, Scottsdale, AZ, United States Department of Hematology, Erasmus Medical Centre, Rotterdam, Netherlands * Corresponding author; email: mulligan{at}mpi.com. The aims of this study were to assess the feasibility of prospective pharmacogenomics research in multicenter international clinical trials of bortezomib in multiple myeloma, and to develop predictive classifiers of response and survival with bortezomib. Patients with relapsed myeloma enrolled in phase II and phase III clinical trials of bortezomib and consented to genomic analyses of pre-treatment tumor samples. Bone marrow aspirates were subject to a negative-selection procedure to enrich for tumor cells, and these samples were utilized for gene expression profiling using DNA microarrays. Data quality and correlations with trial outcomes were assessed by multiple groups. Gene expression in this dataset was consistent with data published from a single-center study of newly diagnosed multiple myeloma. Response and survival classifiers were developed and shown to be significantly associated with outcome via testing on independent data. The survival classifier improved upon the risk stratification provided by the International Staging System. Predictive models and biological correlates of response show some specificity for bortezomib rather than dexamethasone. Informative gene expression data and genomic classifiers that predict clinical outcome can be derived from prospective clinical trials of new anti-cancer agents. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Genomics in myeloma: the philosopher's stone? Andreas Rosenwald Blood 2007 109: 3126. [Full Text] [PDF] This article has been cited by other articles: B. Nair, J. D. Shaughnessy Jr, Y. Zhou, M. Astrid-Cartron, P. Qu, F. van Rhee, E. Anaissie, Y. Alsayed, S. Waheed, K. Hollmig, et al. Gene expression profiling of plasma cells at myeloma relapse from tandem transplantation trial Total Therapy 2 predicts subsequent survival Blood, June 25, 2009; 113(26): 6572 - 6575. [Abstract] [Full Text] [PDF] G. Bianchi, L. Oliva, P. Cascio, N. Pengo, F. Fontana, F. Cerruti, A. Orsi, E. Pasqualetto, A. Mezghrani, V. Calbi, et al. The proteasome load versus capacity balance determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition Blood, March 26, 2009; 113(13): 3040 - 3049. [Abstract] [Full Text] [PDF] M. A. Dawson, S. S. Opat, Y. Taouk, M. Donovan, M. Zammit, K. Monaghan, N. Horvath, A. W. Roberts, H. M. Prince, M. Hertzberg, et al. Clinical and Immunohistochemical Features Associated with a Response to Bortezomib in Patients with Multiple Myeloma Clin. Cancer Res., January 15, 2009; 15(2): 714 - 722. [Abstract] [Full Text] [PDF] M. van Duin, S. S. Sahota, Y. de Knegt, A. Broyl, D. Joseph-Pietras, G. Mulligan, B. Bryant, and P. Sonneveld Expression of Cancer Testis Antigens as Potential Targets for Immunotherapy Is Retained Following Treatment in Multiple Myeloma. Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 1722 - 1722. [Abstract] J. Greshock, J. Cheng, D. Rusnak, A. M. Martin, R. Wooster, T. Gilmer, K. Lee, B. L. Weber, and T. Zaks Genome-wide DNA copy number predictors of lapatinib sensitivity in tumor-derived cell lines Mol. Cancer Ther., April 1, 2008; 7(4): 935 - 943. [Abstract] [Full Text] [PDF] G. J. Ahmann, W. J. Chng, K. J. Henderson, T. L. Price-Troska, R. W. DeGoey, M. M. Timm, A. Dispenzieri, P. R. Greipp, A. Sable-Hunt, L. Bergsagel, et al. Effect of Tissue Shipping on Plasma Cell Isolation, Viability, and RNA Integrity in the Context of a Centralized Good Laboratory Practice-Certified Tissue Banking Facility Cancer Epidemiol. Biomarkers Prev., March 1, 2008; 17(3): 666 - 673. [Abstract] [Full Text] [PDF] R. Piva, B. Ruggeri, M. Williams, G. Costa, I. Tamagno, D. Ferrero, V. Giai, M. Coscia, S. Peola, M. Massaia, et al. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib Blood, March 1, 2008; 111(5): 2765 - 2775. [Abstract] [Full Text] [PDF] W. J. Chng, E. Braggio, G. Mulligan, B. Bryant, E. Remstein, R. Valdez, A. Dogan, and R. Fonseca The centrosome index is a powerful prognostic marker in myeloma and identifies a cohort of patients that might benefit from aurora kinase inhibition Blood, February 1, 2008; 111(3): 1603 - 1609. [Abstract] [Full Text] [PDF] F. Zhan, B. Barlogie, G. Mulligan, J. D. 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