期刊
BLOOD
卷 112, 期 10, 页码 4193-4201出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-02-134411
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资金
- Bundesministerium fur Bildung und Forschung (German National Genome Research Network) [01 GR 0459, 01 GS 0448]
- Deutsche Forschungsgemeinschaft (DFG-German Research Council) [A6, A8]
- National Institutes of Health [CA101140, CA114725, CA077658, CA016058]
- Coleman Leukemia Research Foundation
Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene-expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AM-LCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes), which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P=.002), event-free survival (HR = 1.73; P=.001), and relapse-free survival (HR = 1.76; P=.025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD, and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR = 4.11; P <.001), event-free survival (HR = 2.90; P <.001), and relapse-free survival (HR = 3.14, P <.001) and retained its significance in a multivariate model for OS. In summary, we present a novel gene-expression signature that offers additional prognostic information for patients with CN-AML. (Blood. 2008; 112: 4193-4201)
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