High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression. and chromosome 3q26 abnormalities underestimated

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Abstract

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.
Original languageUndefined/Unknown
Pages (from-to)4329-4337
Number of pages9
JournalBlood
Volume111
Issue number8
DOIs
Publication statusPublished - 2008

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