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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4329-4337. Prepublished online as a Blood First Edition Paper on February 13, 2008; DOI 10.1182/blood-2007-10-119230. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2007-10-119230v1 111/8/4329    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 Lugthart, S. Articles by Delwel, R. Search for Related Content PubMed PubMed Citation Articles by Lugthart, S. Articles by Delwel, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 18, 2007 Accepted January 28, 2008 High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated Sanne Lugthart, Ellen van Drunen, Yvette van Norden, Antoinette van Hoven, Claudia A.J. Erpelinck, Peter J.M. Valk, H. Berna Beverloo, Bob Lowenberg, and Ruud Delwel* Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands Department of Trials and Statistics, Erasmus University Medical Center, Rotterdam, Netherlands * Corresponding author; email: h.delwel{at}erasmusmc.nl. Inappropriate expression of EVI1 (ecotropic virus integration-1), in particular splice-form EVI1-D, through chromosome 3q26 lesions or other mechanisms has been implicated in the development of high-risk acute myeloid leukemia (AML). To validate the clinical relevance of EVI1-1D, as well as of the other EVI1 splice-forms and the related MDS1/EVI1 (ME) gene, real-time RQ-PCR was performed in 534 untreated adults with de novo AML. EVI1-1D was highly expressed in 6% of cases (n=32) whereas 7.8% were EVI1 positive (n=41) for all splice variants. High EVI1 predicted for a distinctly worse event free survival (HR=1.9; P=0.002) and disease free survival (HR=2.1, P=0.006) following multivariate analysis. Importantly, we distinguished a subset of EVI1 positive cases that lacked expression of ME (EVI1+ME-; n=17) from cases that were ME positive (EVI1+ME+; n=24). The atypical EVI1+ME- expression pattern exhibited cytogenetically detectable chromosomal 3q26 breakpoints in eight cases. Florescence in situ hybridization revealed seven more EVI1+ME- cases that carried cryptic 3q26 breakpoints, which were not found in the EVI1+ME+ group. EVI1+ME- expression predicts for an extremely poor prognosis distinguishable from the general EVI1+ AML patients (OS; P<0.001 and EFS; P=0.002). We argue that EVI1/ME quantitative expression analysis should be implemented in the molecular diagnostic procedures of AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Cilloni, A. Renneville, F. Hermitte, R. K. Hills, S. Daly, J. V. Jovanovic, E. Gottardi, M. Fava, S. Schnittger, T. Weiss, et al. Real-Time Quantitative Polymerase Chain Reaction Detection of Minimal Residual Disease by Standardized WT1 Assay to Enhance Risk Stratification in Acute Myeloid Leukemia: A European LeukemiaNet Study J. Clin. Oncol., November 1, 2009; 27(31): 5195 - 5201. [Abstract] [Full Text] [PDF] T. A. Konrad, A. Karger, H. Hackl, I. Schwarzinger, I. Herbacek, and R. Wieser Inducible expression of EVI1 in human myeloid cells causes phenotypes consistent with its role in myelodysplastic syndromes J. Leukoc. Biol., October 1, 2009; 86(4): 813 - 822. [Abstract] [Full Text] [PDF] E. R. Mardis, L. Ding, D. J. Dooling, D. E. Larson, M. D. McLellan, K. Chen, D. C. Koboldt, R. S. Fulton, K. D. Delehaunty, S. D. McGrath, et al. Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome N. Engl. J. Med., September 10, 2009; 361(11): 1058 - 1066. [Abstract] [Full Text] [PDF] S. Schnittger, W. Kern, C. Tschulik, T. Weiss, F. Dicker, B. Falini, C. Haferlach, and T. Haferlach Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML Blood, September 10, 2009; 114(11): 2220 - 2231. [Abstract] [Full Text] [PDF] M. C. Bene and J. S. Kaeda How and why minimal residual disease studies are necessary in leukemia: a review from WP10 and WP12 of the European LeukaemiaNet Haematologica, August 1, 2009; 94(8): 1135 - 1150. [Abstract] [Full Text] [PDF] R. G.W. Verhaak, B. J. Wouters, C. A.J. Erpelinck, S. Abbas, H. B. Beverloo, S. Lugthart, B. Lowenberg, R. Delwel, and P. J.M. Valk Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling Haematologica, January 1, 2009; 94(1): 131 - 134. [Abstract] [Full Text] [PDF] A. De Weer, F. Speleman, B. Cauwelier, N. Van Roy, N. Yigit, B. Verhasselt, B. De Moerloose, Y. Benoit, L. Noens, D. Selleslag, et al. EVI1 overexpression in t(3;17) positive myeloid malignancies results from juxtaposition of EVI1 to the MSI2 locus at 17q22 Haematologica, December 1, 2008; 93(12): 1903 - 1907. [Abstract] [Full Text] [PDF] K. Dohner and H. Dohner Molecular characterization of acute myeloid leukemia Haematologica, July 1, 2008; 93(7): 976 - 982. 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