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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1189-1198.
Prepublished online as a Blood First Edition Paper on May 5, 2005; DOI 10.1182/blood-2004-12-4938.
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Submitted December 30, 2004
Accepted April 24, 2005
A global approach to the diagnosis of leukemia using gene expression profiling
Torsten Haferlach*, Alexander Kohlmann, Susanne Schnittger, Martin Dugas, Wolfgang Hiddemann, Wolfgang Kern, and Claudia Schoch
Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, Munchen, Germany
Department of Medical Informatics, Biometrics and Epidemiology, Ludwig-Maximilians-University, Munchen, Germany
* Corresponding author; email: torsten.haferlach{at}med.uni-muenchen.de.
Accurate diagnosis and classification of leukemias are the bases for the appropriate management of patients. The diagnostic accuracy and efficiency of present methods may be improved by the use of microarrays for gene expression profiling. We analyzed gene expression profiles in bone marrow and peripheral blood samples from 937 patients with all clinically relevant leukemia subtypes (n=892) and non-leukemic controls (n=45) by U133A and B GeneChips (Affymetrix). For each subgroup differentially expressed genes were calculated. Class prediction was performed using support vector machines. Prediction accuracies were estimated by 10-fold cross validation and assessed for robustness in a 100-fold resampling approach using randomly chosen test-sets consisting of 1/3 of the samples. Applying the top 100 genes of each subgroup an overall prediction accuracy of 95.1% was achieved which was confirmed by resampling (median, 93.8%; 95% confidence interval, 91.4%-95.8%). In particular, AML with t(15;17), t(8;21), or inv(16), CLL, and Pro-B-ALL with t(11q23) were classified with 100% sensitivity and 100% specificity. Accordingly, cluster analysis completely separated all of the 13 subgroups analyzed. Gene expression profiling can predict all clinically relevant subentities of leukemia with high accuracy.
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