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Blood, 30 April 2009, Vol. 113, No. 18, pp. 4331-4340. Prepublished online as a Blood First Edition Paper on January 26, 2009; DOI 10.1182/blood-2008-09-178350. This Article Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2008-09-178350v1 113/18/4331    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 Hose, D. Articles by Goldschmidt, H. Search for Related Content PubMed PubMed Citation Articles by Hose, D. Articles by Goldschmidt, H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 10, 2008 Accepted January 7, 2009 Inhibition of Aurora-kinases for tailored risk adapted treatment of multiple myeloma Dirk Hose*, Thierry Reme, Tobias Meissner, Jerome Moreaux, Anja Seckinger, Joe Lewis, Vladimir Benes, Axel Benner, Michael Hundemer, Thomas Hielscher, John D. Shaughnessy Jr., Bart Barlogie, Kai Neben, Alwin Kramer, Jens Hillengass, Uta Bertsch, Anna Jauch, John De Vos, Jean Francois Rossi, Thomas Mohler, Jonathon Blake, Jurgen Zimmermann, Bernard Klein, and Hartmut Goldschmidt Medizinische Klinik V, Universitatsklinikum Heidelberg, Heidelberg, Germany CHU Montpellier, Institute for Research in Biotherapy, Hopital Saint-Eloi, Montpellier, France INSERM U847, Montpellier, France European Molecular Biology Laboratory, Heidelberg, Germany Abteilung fur Biostatistik, Deutsches Krebsforschungszentrum, Heidelberg, Germany Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, United States Institut fur Humangenetik, Universitatsklinikum Heidelberg, Heidelberg, Germany Nationales Centrum fur Tumorerkrankungen, Heidelberg, Germany * Corresponding author; email: dirk.hose{at}med.uni-heidelberg.de. Genetic instability and cellular proliferation have been associated with Aurora-kinase expression in several cancer entities, including multiple myeloma. Therefore, the expression of Aurora-A, -B and -C was determined by Affymetrix DNA-microarrays in 784 samples including two independent sets of 233 and 345 CD138-purified myeloma-cells from previously untreated myeloma-patients. Chromosomal aberrations were assessed by comprehensive iFISH and proliferation of primary myeloma-cells by propidium-iodine staining. The effect of the clinical Aurora-kinase inhibitor VX680 on proliferation of 20 human-myeloma-cell-lines and survival of 5 primary myeloma-cell-samples was tested. We found Aurora-A and -B to be expressed at varying frequencies in primary myeloma-cells of different patient-cohorts, Aurora-C in testis-samples only. Myeloma-cell samples with detectable vs. absent Aurora-A expression show a significantly higher proliferation rate, but neither a higher absolute number of chromosomal aberrations present (aneuploidy) nor of subclonal aberrations (chromosomal instability). VX680 induces apoptosis in all myeloma-cell-line- and primary myeloma-cell-samples tested. Presence of Aurora-A expression delineates significantly inferior event-free and overall-survival in two independent cohorts of patients undergoing high-dose chemotherapy, independent of conventional prognostic factors, i.e. serum-2-microglobulin or ISS-stage. In conclusion, using gene expression profiling, Aurora-kinase inhibitors as promising therapeutic option for newly-diagnosed patients can be tailoredly given to patients with adverse prognosis, expressing Aurora-A. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Hose, J. Moreaux, T. Meissner, A. Seckinger, H. Goldschmidt, A. Benner, K. Mahtouk, J. Hillengass, T. Reme, J. De Vos, et al. Induction of angiogenesis by normal and malignant plasma cells Blood, July 2, 2009; 114(1): 128 - 143. [Abstract] [Full Text] [PDF]

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