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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 Gene Expression Genomics Free Research Articles Neoplasia 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: J. Greshock, J. Cheng, D. Rusnak, A. M. Martin, R. Wooster, T. Gilmer, K. 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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] 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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