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An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia

Metzeler, Klaus H., Hummel, Manuela, Bloomfield, Clara D., Spiekermann, Karsten, Braess, Jan, Sauerland, Maria-Cristina, Heinecke, Achim, Radmacher, Michael, Marcucci, Guido, Whitman, Susan P., Maharry, Kati, Paschka, Peter, Larson, Richard A., Berdel, Wolfgang E., Büchner, Thomas, Wörmann, Bernhard, Mansmann, Ulrich, Hiddemann, Wolfgang, Bohlander, Stefan K., Buske, Christian·2008·Blood
DOI 10.1182/blood-2008-02-134411
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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.

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Cited by

Metadata

Authors
Metzeler, K. H., Hummel, M., Bloomfield, C. D., Spiekermann, K., Braess, J., Sauerland, M.-C., Heinecke, A., Radmacher, M., Marcucci, G., Whitman, S. P., Maharry, K., Paschka, P., Larson, R. A., Berdel, W. E., Büchner, T., Wörmann, B., Mansmann, U., Hiddemann, W., Bohlander, S. K., & Buske, C.
Affiliations
  • Laboratory of Leukemia Diagnostics, Department of Internal Medicine III, Ludwig-Maximilians-Universität, Campus Groβhadern and
  • Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany;
  • Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, Ohio State University, Columbus;
  • Department of Medical Informatics and Biomathematics, University of Münster, Münster, Germany;
  • University of Chicago, IL;
  • Department of Internal Medicine A, Hematology and Oncology, University of Münster, Münster, Germany; and
  • Department of Hematology and Oncology, Municipal Hospital, Braunschweig, Germany
Venue
Blood
Publisher
American Society of Hematology
Published
2008-11-15
Volume
112
Issue
10
Pages
4193-4201
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2008-02-134411
Cited by
363
References
3
Language
en

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