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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3669-3675. Prepublished online as a Blood First Edition Paper on December 22, 2005; DOI 10.1182/blood-2005-09-3810. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-09-3810v1 107/9/3669    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 Chng, W. J. Articles by Fonseca, R. Search for Related Content PubMed PubMed Citation Articles by Chng, W. J. Articles by Fonseca, R. Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Clinical implication of centrosome amplification in plasma cell neoplasm Wee J. Chng, Greg J. Ahmann, Kim Henderson, Rafael Santana-Davila, Philip R. Greipp, Morie A. Gertz, Martha Q. Lacy, Angela Dispenzieri, Shaji Kumar, S. Vincent Rajkumar, John A. Lust, Robert A. Kyle, Steven R. Zeldenrust, Suzanne R. Hayman, and Rafael Fonseca From the Division of Hematology-Oncology, Mayo Clinic, Scottsdale, AZ; the Division of Hematology, Mayo Clinic Rochester and Mayo Clinic Comprehensive Cancer Center, Rochester, MN; the Department of Hematology-Oncology, National University Hospital, Singapore. The mechanisms underlying aneuploidy in multiple myeloma (MM) are unclear. Centrosome amplification has been implicated as the cause of chromosomal instability in a variety of tumors and is a potential mechanism causing aneuploidy in MM. Using immunofluorescent (IF) staining, centrosome amplification was detected in 67% of monoclonal gammopathies, including monoclonal gammopathy of undetermined significance (MGUS). We also investigated the gene expression of centrosome proteins. Overall, gene expression data correlated well with IF-detected centrosome amplification, allowing us to derive a gene expression-based centrosome index (CI) as a surrogate for centrosome amplification. Clinically, MM patients with high CI (> 4) are associated with poor prognostic genetic and clinical subtypes (chromosome 13 deletion, t(4; 14), t(14;16), and PCLI > 1%, P < .05) and are shown here to have short survival (11.1 months versus 39.1 months, P < .001). On multivariate regression, a high CI is an independent prognostic factor. Given that centrosome amplification is already observed in MGUS and probably integral to early chromosomal instability and myeloma genesis, and patients with more extensive centrosome amplification have shorter survival, the mechanisms leading to centrosome amplification should be investigated because these may offer new avenues for therapeutic intervention. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] 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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