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Prepublished online as a Blood First Edition Paper on October 3, 2002; DOI 10.1182/blood-2002-05-1459.

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Blood, 1 February 2003, Vol. 101, No. 3, pp. 837-845

CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients

Sahar Barjesteh van Waalwijk van Doorn-Khosrovani, Claudia Erpelinck, Wim L. J. van Putten, Peter J. M. Valk, Sonja van der Poel-van de Luytgaarde, Ronald Hack, Rosalyn Slater, Elisabeth M. E. Smit, H. Berna Beverloo, Gregor Verhoef, Leo F. Verdonck, Gert J. Ossenkoppele, Pieter Sonneveld, Georgine E. de Greef, Bob Löwenberg, and Ruud Delwel

From the Institute of Hematology, Erasmus Medical Centre, Rotterdam, Netherlands; the Department of Cell Biology and Genetics, Erasmus Medical Centre, Rotterdam, Netherlands; the Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, Netherlands; the Department of Hematology, Vrije Universiteit Medical Centre, Amsterdam, Netherlands; the Department of Hematology, University Medical Centre, Utrecht, Netherlands; and the Department of Hematology, University Hospitals, Katholieke Universiteit Leuven, Leuven, Belgium.

The proto-oncogene EVI1 encodes a DNA binding protein and is located on chromosome 3q26. The gene is aberrantly expressed in acute myeloid leukemia (AML) patients carrying 3q26 abnormalities. Two mRNAs are transcribed from this locus: EVI1 and a fusion of EVI1 with MDS1 (MDS1-EVI1), a gene located 5' of EVI1. The purpose of this study was to investigate which of the 2 gene products is involved in transformation in human AML. To discriminate between EVI1 and MDS1-EVI1 transcripts, distinct real-time quantitative polymerase chain reaction (PCR) assays were developed. Patients with 3q26 abnormalities often showed high EVI1 and MDS1-EVI1 expression. In a cohort of 319 AML patients, 4 subgroups could be distinguished: EVI1+ and MDS1-EVI1- (6 patients; group I), EVI1+ and MDS1-EVI1+ (26 patients; group II), EVI1- and MDS1-EVI1+ (12 patients; group III), and EVI1- and MDS1-EVI1- (275 patients; group IV). The only 4 patients with a 3q26 aberration belonged to groups I and II. Interestingly, high EVI1 and not MDS1-EVI1 expression was associated with unfavorable karyotypes (eg, -7/7q-) or complex karyotypes. Moreover, a significant correlation was observed between EVI1 expression and 11q23 aberrations (mixed lineage leukemia [MLL] gene involvement). Patients from groups I and II had significantly shorter overall and event-free survival than patients in groups III and IV. Our data demonstrate that high EVI1 expression is an independent poor prognostic marker within the intermediate- risk karyotypic group.

© 2003 by The American Society of Hematology.
 

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