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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2276-2284. Prepublished online as a Blood First Edition Paper on November 14, 2006; DOI 10.1182/blood-2006-07-038430. This Article Full Text (PDF) All Versions of this Article: blood-2006-07-038430v1 109/6/2276    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, Jr, J. D Articles by Barlogie, B. Search for Related Content PubMed PubMed Citation Articles by Shaughnessy, Jr, J. D Articles by Barlogie, B. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 31, 2006 Accepted October 27, 2006 A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1 John D Shaughnessy, Jr*, Fenghuang Zhan, Bart E Burington, Yongsheng Huang, Simona Colla, Ichiro Hanamura, James P Stewart, Bob Kordsmeier, Christopher Randolph, David R Williams, Yan Xiao, Hongwei Xu, Joshua Epstein, Elias Anaissie, Somashekar G Krishna, Michele Cottler-Fox, Klaus Hollmig, Abid Mohiuddin, Mauricio Pineda-Roman, Guido Tricot, Frits van Rhee, Jeffrey Sawyer, Yazan Alsayed, Ronald Walker, Maurizio Zangari, John Crowley, and Bart Barlogie University of Arkansas for Medical Sciences, Little Rock, AR Cancer Research and Biostatistics, Seattle, WA * Corresponding author; email: shaughnessyjohn{at}uams.edu. To molecularly define high-risk disease, we performed microarray analysis on tumor cells from 532 newly diagnosed patients with multiple myeloma (MM) treated on two separate protocols. Using log rank tests of expression quartiles, 70 genes, 30% mapping to chromosome 1 (P < .001), were linked to early disease-related death. Importantly, the majority of up-regulated genes mapped to chromosome 1q and of down-regulated genes mapped to chromosome 1p. The ratio of mean expression levels of up- to down-regulated genes defined a high-risk score present in 13% of patients with shorter durations of complete remission, event-free and overall survival (training set: HR 5.16, P < .0001; test cohort: HR 4.75, P < .0001). The high-risk score also was an independent predictor of outcome endpoints in multivariate analysis (P < .0001) that included the International Staging System and high-risk translocations. In a comparison of paired baseline and relapse samples, the high-risk score frequency rose to 76% at relapse and predicted short post-relapse survival (P < .05). Multivariate discriminant analysis revealed that a 17-gene subset could predict outcome a well as the 70-gene model. Our data suggest that altered transcriptional regulation of genes mapping to chromosome 1 may contribute to disease progression and that expression profiling can be used to identify high-risk disease and guide therapeutic interventions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: 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 Fenghuang Zhan, Bart Barlogie, George Mulligan, John D. Shaughnessy, Jr, and Barb Bryant Blood 2008 111: 968-969. [Full Text] [PDF] CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms Fenghuang Zhan, Simona Colla, Xiaosong Wu, Bangzheng Chen, James P. Stewart, W. Michael Kuehl, Bart Barlogie, and John D. Shaughnessy, Jr Blood 2007 109: 4995-5001. [Abstract] [Full Text] [PDF] This article has been cited by other articles: J. Shi, G. J. Tricot, T. K. Garg, P. A. Malaviarachchi, S. M. Szmania, R. E. Kellum, B. Storrie, A. Mulder, J. D. Shaughnessy Jr, B. Barlogie, et al. Bortezomib down-regulates the cell-surface expression of HLA class I and enhances natural killer cell-mediated lysis of myeloma Blood, February 1, 2008; 111(3): 1309 - 1317. [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] U.-M. Fagerli, R. U. Holt, T. Holien, T. K. Vaatsveen, F. Zhan, K. W. Egeberg, B. Barlogie, A. Waage, H. Aarset, H. Y. Dai, et al. Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells Blood, January 15, 2008; 111(2): 806 - 815. [Abstract] [Full Text] [PDF] B. Barlogie, G. Tricot, J. Haessler, F. van Rhee, M. Cottler-Fox, E. Anaissie, J. Waldron, M. Pineda-Roman, R. Thertulien, M. Zangari, et al. Cytogenetically defined myelodysplasia after melphalan-based autotransplantation for multiple myeloma linked to poor hematopoietic stem-cell mobilization: the Arkansas experience in more than 3000 patients treated since 1989 Blood, January 1, 2008; 111(1): 94 - 100. [Abstract] [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] J. Haessler, J. D. Shaughnessy Jr., F. Zhan, J. Crowley, J. Epstein, F. van Rhee, E. Anaissie, M. Pineda-Roman, M. Zangari, K. Hollmig, et al. Benefit of Complete Response in Multiple Myeloma Limited to High-Risk Subgroup Identified by Gene Expression Profiling Clin. Cancer Res., December 1, 2007; 13(23): 7073 - 7079. [Abstract] [Full Text] [PDF] J. Davidsson, A. Andersson, K. Paulsson, M. Heidenblad, M. Isaksson, A. Borg, J. Heldrup, M. Behrendtz, I. Panagopoulos, T. Fioretos, et al. Tiling resolution array comparative genomic hybridization, expression and methylation analyses of dup(1q) in Burkitt lymphomas and pediatric high hyperdiploid acute lymphoblastic leukemias reveal clustered near-centromeric breakpoints and overexpression of genes in 1q22-32.3 Hum. Mol. Genet., September 15, 2007; 16(18): 2215 - 2225. [Abstract] [Full Text] [PDF] H. K. Prasad, F. Zhan, J. Shaughnessy, D. Focosi, A. T. Andrews, R. A. Kyle, and S. V. Rajkumar Smoldering Multiple Myeloma N. Engl. J. Med., September 6, 2007; 357(10): 1048 - 1050. [Full Text] [PDF] J. A. Katzel, P. Hari, and D. H. Vesole Multiple Myeloma: Charging Toward a Bright Future CA Cancer J Clin, September 1, 2007; 57(5): 301 - 318. [Abstract] [Full Text] [PDF] F. van Rhee, J. Crowley, B. Barlogie, S. V. Rajkumar, R. A. Kyle, P. Moreau, J.-L. Harousseau, M. Attal, B. Bruno, G. Ciccone, et al. Allografting or Autografting for Myeloma N. Engl. J. Med., June 21, 2007; 356(25): 2646 - 2648. [Full Text] [PDF] F. Zhan, S. Colla, X. Wu, B. Chen, J. P. Stewart, W. M. Kuehl, B. Barlogie, and J. D. Shaughnessy Jr CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms Blood, June 1, 2007; 109(11): 4995 - 5001. [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] M. Attal, P. Moreau, H. Avet-Loiseau, and J.-L. Harousseau Stem Cell Transplantation in Multiple Myeloma Hematology, January 1, 2007; 2007(1): 311 - 316. [Abstract] [Full Text] [PDF]

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