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...
| Publicado en: | Journal of Clinical Oncology Vol. 27; no. 30; pp. 5031 - 5039 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
American Society of Clinical Oncology
10/20/2009
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105231663&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105231663 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 0732183X 20D jtl: Journal of Clinical Oncology issn: 0732183X maglogo: N pubinfo: dt: 10/20/2009 vid: 27 iid: 30 pid: 26892 pub: American Society of Clinical Oncology place: Alexandria, Virginia artinfo: ui: 105231663 105231663 NLM19752345 2010444876 10.1200/JCO.2008.20.5328 NLM19752345 105231663 ppf: 5031 ppct: 8 formats: tig: 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 refInfo: holdings: @attributes: islocal: N |
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