High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities.
J Clin Oncol
; 28(12): 2101-7, 2010 Apr 20.
Article
em En
| MEDLINE
| ID: mdl-20308656
ABSTRACT
PURPOSE The purpose of this study was to investigate frequency and prognostic significance of high EVI1 expression in acute myeloid leukemia (AML). PATIENTS AND METHODS A diagnostic assay detecting multiple EVI1 splice variants was developed to determine the relative EVI1 expression by single real-time quantitative polymerase chain reaction in 1,382 newly diagnosed adult patients with AML younger than 60 years. Patients were treated on four Dutch-Belgian HOVON (n = 458) and two German-Austrian AML Study Group protocols (n = 924). Results The EVI1 assay was tested in the HOVON cohort and validated in the AMLSG cohort. High EVI1 levels (EVI1(+)) were found with similar frequencies in both cohorts combined, with a 10.7% incidence (148 of 1,382). EVI1(+) independently predicted low complete remission (CR) rate (odds ratio, 0.54; P = .002), adverse relapse-free survival (RFS; hazard ratio [HR], 1.32; P = .05), and event-free survival (EFS; HR, 1.46; P < .001). This adverse prognostic impact was more pronounced in the intermediate cytogenetic risk group (EFS; HR, 1.64; P < .001; and RFS; HR, 1.55; P = .02), and was also apparent in cytogenetically normal AML (EFS; HR, 1.67; P = .008). Besides inv(3)/t(3;3), EVI1(+) was significantly associated with chromosome abnormalities monosomy 7 and t(11q23), conferring prognostic impact within these two cytogenetic subsets. EVI1(+) was virtually absent in favorable-risk AML and AML with NPM1 mutations. Patients with EVI1(+) AML (n = 28) who received allogeneic stem cell transplantation in first CR had significantly better 5-year RFS (33% +/- 10% v 0%). CONCLUSION EVI1 expression in AML is unequally distributed in cytogenetic subtypes. It predicts poor outcome, particularly among intermediate cytogenetic risk AML. Patients with EVI1(+) AML may benefit from allogeneic transplantation in first CR. Pretreatment EVI1 screening should be included in risk stratification.
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MEDLINE
Assunto principal:
Fatores de Transcrição
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Translocação Genética
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Cromossomos Humanos Par 7
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Cromossomos Humanos Par 11
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Proto-Oncogenes
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Leucemia Mieloide Aguda
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Proteínas de Ligação a DNA
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Monossomia
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article