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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1603-1609. Prepublished online as a Blood First Edition Paper on November 15, 2007; DOI 10.1182/blood-2007-06-097774. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2007-06-097774v1 111/3/1603    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 Chng, W. J Articles by Fonseca, R. Search for Related Content PubMed PubMed Citation Articles by Chng, W. J Articles by Fonseca, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 26, 2007 Accepted October 30, 2007 The centrosome index is a powerful prognostic marker in myeloma and identifies a cohort of patients that may benefit from aurora kinase inhibition Wee J Chng*, Esteben Braggio, George Mulligan, Barbara Bryant, Ellen Remstein, Riccardo Valdez, Ahment Dogan, and Rafael Fonseca Department of Hematology-Oncology, Mayo Clinic, Scottsdale, AZ, United States Oncology Clinical Development, Millennium Pharmaceuticals, Inc., Cambridge, MA, United States Department of Pathology, Mayo Clinic, Rochester, MN, United States Department of Pathology, Mayo Clinic, Scottsdale, AZ, United States * Corresponding author; email: wee_joo_chng{at}nuh.com.sg. Centrosome amplification is common in myeloma and may be involved in disease pathogenesis. We have previously derived a gene expression-based centrosome index (CI) that correlated with centrosome amplification and was an independent prognostic factor in a small cohort of heterogeneously treated patients. In this study, we validated the prognostic significance of the CI in 2 large cohorts of patients entered into clinical trials and showed that a high CI is a powerful independent prognostic factor in both newly diagnosed and relapsed patients whether treated by intensive therapy (total therapy II) or novel agents (bortezomib). Tumors with high CI over-expressed genes coding for proteins involved in cell cycle, proliferation, DNA damage and G2-M checkpoints, and associated with the centrosome and kinetochore / microtubules. In particular, aurora kinases are significantly over-expressed in patients with high CI, with concordant increase in protein expression. Human myeloma cell lines with higher CI are more responsive to treatment with a novel aurora kinase inhibitor. Aurora kinase may represent novel therapeutic targets in these patients with very poor prognosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Hose, T. Reme, T. Meissner, J. Moreaux, A. Seckinger, J. Lewis, V. Benes, A. Benner, M. Hundemer, T. Hielscher, et al. Inhibition of aurora kinases for tailored risk-adapted treatment of multiple myeloma Blood, April 30, 2009; 113(18): 4331 - 4340. [Abstract] [Full Text] [PDF] C. A. Maxwell, M. C. Fleisch, S. V. Costes, A. C. Erickson, A. Boissiere, R. Gupta, S. A. Ravani, B. Parvin, and M. H. Barcellos-Hoff Targeted and Nontargeted Effects of Ionizing Radiation That Impact Genomic Instability Cancer Res., October 15, 2008; 68(20): 8304 - 8311. [Abstract] [Full Text] [PDF]

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