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Metzeler, K.H. ; Dufour, A. ; Benthaus, T. ; Hummel, M. ; Sauerland, M.C. ; Heinecke, A. ; Berdel, W.E. ; Büchner, T. ; Wörmann, B. ; Mansmann, U. ; Braess, J. ; Spiekermann, K. ; Hiddemann, W. ; Buske, C. ; Bohlander, S.K.

ERG expression is an independent prognostic factor and allows refined risk stratification in cytogenetically normal acute myeloid leukemia: A comprehensive analysis of ERG, MN1, and BAALC transcript levels using oligonucleotide microarrays.

J. Clin. Oncol. 27, 5031-5038 (2009)
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Purpose: Recently, several novel molecular prognostic markers were identified in cytogenetically normal acute myeloid leukemia (CN-AML). In addition to the well-known influence of FLT3, NPM1, and CEBPA mutations, high transcript levels of the ERG, BAALC, and MN1 genes have been associated with inferior outcomes, but the relative importance of these risk markers remains to be defined. - Patients and Methods: We analyzed ERG, BAALC, and MN1 expression levels in a cohort of 210 patients with CN-AML who received intensive chemotherapy. Expression levels of ERG, BAALC, and MN1 were determined in bone marrow samples by using oligonucleotide microarrays. - Results: High transcript levels of ERG, BAALC, and MN1 were predictors for inferior overall survival (OS) and a lower rate of complete remissions (CRs). There were significant positive correlations between the expression levels of all three genes. ERG expression levels predicted OS in elderly patients (ie, age 60 years or older) with CN-AML (P = .006) as well as in younger patients (P = .013). In multivariate analyses, high ERG expression was independently associated with a lower CR rate (P = .013), shorter event-free survival (P = .008), and shorter OS (P = .005). Patients who had low ERG levels and absent FLT3 internal tandem duplication (ITD) had a 5-year OS of 44%, and patients who had high ERG expression and FLT3 ITD had a 5-year OS of only 5%. - Conclusion: We analyzed a comprehensive set of molecular risk factors in a large, homogeneous CN-AML patient cohort. In this study, high ERG expression levels emerged as a strong negative prognostic factor and provided prognostic information in addition to established molecular markers.
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Publication type Article: Journal article
Document type Scientific Article
Keywords internal tandem duplications; high-dose cytarabine; ets-related gene; group-b; normal karyotype; prolonged maintenance; favorable prognosis; microrna expression; prostate-cancer; cebpa mutations
Language english
Publication Year 2009
HGF-reported in Year 0
ISSN (print) / ISBN 0732-183X
e-ISSN 1527-7755
Journal Journal of Clinical Oncology - JCO
Quellenangaben Volume: 27, Issue: 30, Pages: 5031-5038 Article Number: , Supplement: ,
Publisher American Society of Clinical Oncology
Publishing Place Alexandria, USA
Reviewing status Peer reviewed
Institute(s) CCG Pathogenesis of Acute Myeloid Leukemia (KKG-KPL)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-521000-001
PubMed ID 19752345
DOI 10.1200/JCO.2008.20.5328
Erfassungsdatum 2009-12-31
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