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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.

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 infer...

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Published in:Journal of Clinical Oncology Vol. 27; no. 30; pp. 5031 - 5039
Main Authors: Metzeler KH, Dufour A, Benthaus T, Hummel M, Sauerland MC, Heinecke A, Berdel WE, Büchner T, Wörmann B, Mansmann U, Braess J, Spiekermann K, Hiddemann W, Buske C, Bohlander SK, Metzeler, Klaus H, Dufour, Annika, Benthaus, Tobias, Hummel, Manuela, Sauerland, Maria-Cristina
Format: research Journal Article
Published: American Society of Clinical Oncology 10/20/2009
Online Access:View this record in EBSCOhost
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        0732183X
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      jtl: Journal of Clinical Oncology
      issn: 0732183X
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      dt: 10/20/2009
      vid: 27
      iid: 30
      pid: 26892
      pub: American Society of Clinical Oncology
      place: Alexandria, Virginia
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        105231663
        105231663
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        2010444876
        10.1200/JCO.2008.20.5328
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        atl: 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.
      aug:
        au:
          Metzeler KH
          Dufour A
          Benthaus T
          Hummel M
          Sauerland MC
          Heinecke A
          Berdel WE
          Büchner T
          Wörmann B
          Mansmann U
          Braess J
          Spiekermann K
          Hiddemann W
          Buske C
          Bohlander SK
          Metzeler, Klaus H
          Dufour, Annika
          Benthaus, Tobias
          Hummel, Manuela
          Sauerland, Maria-Cristina
        affil: Department of Internal Medicine III, Institute for Medical Informatics, Biometry, and Epidemiology, University Hospital Grosshadern, Ludwig-Maximilians Universität, München, Germany
      sug:
        subj:
          Leukemia, Myeloid, Acute
          Proteins
          Adolescence
          Adult
          Aged
          Aged, 80 and Over
          Prospective Studies
          Female
          Genetic Techniques
          Human
          Leukemia, Myeloid, Acute Drug Therapy
          Male
          Middle Age
          Biochips
          Prognosis
          Risk Assessment
          Risk Factors
          Survival Analysis
          RNA
          Young Adult
          Adolescent: 13-18 years
          Adult: 19-44 years
          Aged: 65+ years
          Aged, 80 & over
          Middle Aged: 45-64 years
          Female
          Male
      ab: 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.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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