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 Löwenberg and Ruud Delwel


Inappropriate expression of EVI1 (ecotropic virus integration-1), in particular splice form EVI1-1D, 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 quantitative polymerase chain reaction 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+ (n = 41) when all splice variants were taken into account. High EVI1 predicted a distinctly worse event-free survival (HR = 1.9; P = .002) and disease-free survival (HR = 2.1, P = .006) following multivariate analysis. Importantly, we distinguished a subset of EVI1+ cases that lacked expression of ME (EVI1+ME; n = 17) from cases that were ME+ (EVI1+ME+; n = 24). The atypical EVI1+ME expression pattern exhibited cytogenetically detectable chromosomal 3q26 breakpoints in 8 cases. Fluorescence in situ hybridization revealed 7 more EVI1+ME cases that carried cryptic 3q26 breakpoints, which were not found in the EVI1+ME+ group. EVI1+ME expression predicts an extremely poor prognosis distinguishable from the general EVI1+ AML patients (overall survival [OS]: P < .001 and event-free survival [EFS]: P = .002). We argue that EVI1/ME quantitative expression analysis should be implemented in the molecular diagnostic procedures of AML.

  • Submitted October 18, 2007.
  • Accepted January 28, 2008.
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