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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 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 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 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 Neoplasia Gene Expression Genomics Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib George Mulligan1, Constantine Mitsiades2, Barb Bryant1, Fenghuang Zhan3, Wee J. Chng4, Steven Roels1, Erik Koenig1, Andrew Fergus1, Yongsheng Huang3, Paul Richardson2, William L. Trepicchio1, Annemiek Broyl5, Pieter Sonneveld5, John D. Shaughnessy, Jr3, P. Leif Bergsagel4, David Schenkein1, Dixie-Lee Esseltine1, Anthony Boral1, and Kenneth C. Anderson2 1 Millennium Pharmaceuticals, Cambridge, MA; 2 Dana-Farber Cancer Institute, Boston, MA; 3 Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock; 4 Mayo Clinic, Scottsdale, AZ; 5 Department of Hematology, Erasmus Medical Centre, Rotterdam, The Netherlands 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 2 and phase 3 clinical trials of bortezomib and consented to genomic analyses of pretreatment tumor samples. Bone marrow aspirates were subject to a negative-selection procedure to enrich for tumor cells, and these samples were used 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 on the risk stratification provided by the International Staging System. Predictive models and biologic 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 anticancer 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: A. Anguiano, S. A. Tuchman, C. Acharya, K. Salter, C. Gasparetto, F. Zhan, M. Dhodapkar, J. Nevins, B. Barlogie, J. D. Shaughnessy Jr, et al. Gene Expression Profiles of Tumor Biology Provide a Novel Approach to Prognosis and May Guide the Selection of Therapeutic Targets in Multiple Myeloma J. Clin. Oncol., September 1, 2009; 27(25): 4197 - 4203. [Abstract] [Full Text] [PDF] P. G. Richardson, W. Xie, C. Mitsiades, A. A. Chanan-Khan, S. Lonial, H. Hassoun, D. E. Avigan, A. L. Oaklander, D. J. Kuter, P. Y. Wen, et al. Single-Agent Bortezomib in Previously Untreated Multiple Myeloma: Efficacy, Characterization of Peripheral Neuropathy, and Molecular Correlations With Response and Neuropathy J. Clin. Oncol., July 20, 2009; 27(21): 3518 - 3525. [Abstract] [Full Text] [PDF] 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] O. Decaux, L. Lode, F. Magrangeas, C. Charbonnel, W. Gouraud, P. Jezequel, M. Attal, J.-L. Harousseau, P. Moreau, R. Bataille, et al. Prediction of Survival in Multiple Myeloma Based on Gene Expression Profiles Reveals Cell Cycle and Chromosomal Instability Signatures in High-Risk Patients and Hyperdiploid Signatures in Low-Risk Patients: A Study of the Intergroupe Francophone du Myelome J. Clin. Oncol., October 10, 2008; 26(29): 4798 - 4805. [Abstract] [Full Text] [PDF] G. Tonon and K. C. Anderson Moving Toward Individualized Cancer Therapies Clin. Cancer Res., August 1, 2008; 14(15): 4682 - 4684. [Abstract] [Full Text] [PDF] B. Burington, B. Barlogie, F. Zhan, J. Crowley, and J. D. Shaughnessy Jr. Tumor Cell Gene Expression Changes Following Short-term In vivo Exposure to Single Agent Chemotherapeutics are Related to Survival in Multiple Myeloma Clin. Cancer Res., August 1, 2008; 14(15): 4821 - 4829. [Abstract] [Full Text] [PDF] 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. Shaughnessy Jr, and B. Bryant High-risk myeloma: a gene expression based risk-stratification model for newly diagnosed multiple myeloma treated with high-dose therapy is predictive of outcome in relapsed disease treated with single-agent bortezomib or high-dose dexamethasone Blood, January 15, 2008; 111(2): 968 - 969. [Full Text] [PDF] N. C. Munshi Investigative Tools for Diagnosis and Management Hematology, January 1, 2008; 2008(1): 298 - 305. [Abstract] [Full Text] [PDF] K. Mahtouk, D. Hose, J. De Vos, J. Moreaux, M. Jourdan, J. F. Rossi, T. Reme, H. Goldschmidt, and B. Klein Input of DNA Microarrays to Identify Novel Mechanisms in Multiple Myeloma Biology and Therapeutic Applications Clin. Cancer Res., December 15, 2007; 13(24): 7289 - 7295. [Abstract] [Full Text] [PDF] W. J. Chng, G. Mulligan, B. Bryant, and L. Bergsagel Survival of genetic subtypes of relapsed myeloma may be modulated by secondary events Blood, April 15, 2007; 109(8): 3610 - 3611. [Full Text] [PDF] R. Fonseca Strategies for Risk-Adapted Therapy in Myeloma Hematology, January 1, 2007; 2007(1): 304 - 310. [Abstract] [Full Text] [PDF]

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