Risk stratification of intermediate-risk acute myeloid leukemia: integrative analysis of a multitude of gene mutation and gene expression markers.
Blood
; 118(4): 1069-76, 2011 Jul 28.
Article
em En
| MEDLINE
| ID: mdl-21596848
ABSTRACT
Numerous molecular markers have been recently discovered as potential prognostic factors in acute myeloid leukemia (AML). It has become of critical importance to thoroughly evaluate their interrelationships and relative prognostic importance. Gene expression profiling was conducted in a well-characterized cohort of 439 AML patients (age < 60 years) to determine expression levels of EVI1, WT1, BCL2, ABCB1, BAALC, FLT3, CD34, INDO, ERG and MN1. A variety of AML-specific mutations were evaluated, that is, FLT3, NPM1, N-RAS, K-RAS, IDH1, IDH2, and CEBPA(DM/SM) (double/single). Univariable survival analysis shows that (1) patients with FLT3(ITD) mutations have inferior overall survival (OS) and event-free survival (EFS), whereas CEBPA(DM) and NPM1 mutations indicate favorable OS and EFS in intermediate-risk AML, and (2) high transcript levels of BAALC, CD34, MN1, EVl1, and ERG predict inferior OS and EFS. In multivariable survival analysis, CD34, ERG, and CEBPA(DM) remain significant. Using survival tree and regression methodologies, we show that CEBPA(DM), CD34, and IDH2 mutations are capable of separating the intermediate group into 2 AML subgroups with highly distinctive survival characteristics (OS at 60 months 51.9% vs 14.9%). The integrated statistical approach demonstrates that from the multitude of biomarkers a greatly condensed subset can be selected for improved stratification of intermediate-risk AML.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
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Biomarcadores Tumorais
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Perfilação da Expressão Gênica
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Blood
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Holanda