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Prepublished online as a Blood First Edition Paper on January 16, 2003; DOI 10.1182/blood-2002-09-2873. This Article Full Text (PDF) All Versions of this Article: 2002-09-2873v1 101/10/3849    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 Shaughnessy, J. Articles by Tricot, G. Search for Related Content PubMed PubMed Citation Articles by Shaughnessy, J. Articles by Tricot, G. Social Bookmarking                   What's this? Submitted September 20, 2002 Accepted January 4, 2003 Continuous absence of metaphase-defined cytogenetic abnormalities especially of chromosome 13 and hypodiploidy assures long-term survival in multiple myeloma treated with total therapy I: interpretation in the context of global gene expression John Shaughnessy, Bart Barlogie*, Jeff Sawyer, Jason McCoy, Anthanasios Fassas, Fenghuang Zhan, Klaus Bumm, Joshua Epstein, Elias Anaissie, Sundar Jagannath, David Vesole, David Siegel, Raman Desikan, Nikhil Munshi, Ashraf Badros, Erming Tian, Maurizio Zangari, Joth Jacobson, John Crowley, and Guido Tricot Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA Department of Cancer Research and Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Universitats-HNO-Klinik, Erlagen, Germany St Vincent Comprehensive Cancer Center, New York, NY, USA Hackensack University Medical Center, Hackensack, NJ, USA Dana Farber Cancer Center, Harvard Medical Center, Boston, MA, USA Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA * Corresponding author; email: barlogiebart{at}uams.edu. Metaphase cytogenetic abnormalities (CA), especially of chromosome 13 (CA 13), confer a grave prognosis in multiple myeloma (MM) even with tandem autotransplants as applied in Total Therapy I, which enrolled 231 patients between 1989 and 1994. With a median follow-up of almost 9 years, the prognostic implications of all individual CA, detected prior to treatment and at relapse, were investigated. Among all CA and standard prognostic factors (SPF) examined prior to therapy, only hypodiploidy and CA 13 (hypo-13 CA), alone or in combination, were associated with shortest event-free survival (EFS) and overall survival (OS). Similarly, the shortest post-relapse OS was observed with hypo-13 CA, which was newly detected in 18 of all 28 patients presenting with this abnormality at relapse. Conversely, superior prognosis was associated with the absence of any CA both at diagnosis and at relapse (10 yr OS, 40%). The lack of independent prognostic implications of other CA points to a uniquely aggressive behavior of hypo-13 CA (present in 16% of patients at diagnosis). Using microarray data in 146 patients enrolled in Total Therapy II, over-expression of cell cycle genes distinguished CA from no CA, especially in cases of del 13 detected by interphase FISH. FISH 13, resulting in a haplo-insufficiency of RB1 and other genes mapping to chromosome 13, as well as activation of IGF1R, appears to have an amplifying effect on cell cycle gene expression, thus providing a molecular explanation for the dire outcome of patients with CA 13 compared to those with other CA. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Barlogie, J. D. Shaughnessy Jr., and J. Crowley Duration of Survival in Patients with Myeloma Treated with Thalidomide N. Engl. J. Med., July 10, 2008; 359(2): 210 - 212. [Full Text] [PDF] J. Haessler, J. 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