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An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia.
- Source :
-
Blood [Blood] 2008 Nov 15; Vol. 112 (10), pp. 4193-201. Date of Electronic Publication: 2008 Aug 20. - Publication Year :
- 2008
-
Abstract
- 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 AMLCG 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.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Disease-Free Survival
Female
Humans
Leukemia, Myeloid, Acute genetics
Male
Middle Aged
Neoplasm Proteins genetics
Nuclear Proteins biosynthesis
Nuclear Proteins genetics
Nucleophosmin
Predictive Value of Tests
Survival Rate
fms-Like Tyrosine Kinase 3 biosynthesis
fms-Like Tyrosine Kinase 3 genetics
DNA Probes chemistry
DNA Probes genetics
Gene Expression Profiling methods
Leukemia, Myeloid, Acute metabolism
Leukemia, Myeloid, Acute mortality
Neoplasm Proteins biosynthesis
Oligonucleotide Array Sequence Analysis methods
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 112
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 18716133
- Full Text :
- https://doi.org/10.1182/blood-2008-02-134411