An eight-gene expression signature for the prediction of survival and time to treatment in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a common and heterogeneous disease. An accurate prediction of outcome is highly relevant for the development of personalized treatment strategies. Microarray technology was shown to be a useful tool for the development of prognostic gene expression scores. However, there are no gene expression scores which are able to predict overall survival in CLL based on the expression of few genes that are better than established prognostic markers. We correlated 151 CLL microarray data sets with overall survival using Cox regression and supervised principal component analysis to derive a prognostic score. This score based on the expression levels of eight genes and was validated in an independent group of 149 CLL patients by quantitative real time PCR. The score was predictive for overall survival and time to treatment in univariate Cox regression in the validation data set (both: p<0.001) and in a multivariate analysis after adjustment for 17p and 11q deletions and the IgVH-status. The score achieved superior prognostic accuracy compared to models based on genomic aberrations and IgVH-status and may support personalized therapy.

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Herold T, Jurinovic V, Metzeler KH, Boulesteix AL, Bergmann M, Seiler T, Mulaw M, Thoene S, Dufour A, Pasalic Z, Schmidberger M, Schmidt M, Schneider S, Kakadia PM, Feuring-Buske M, Braess J, Spiekermann K, Mansmann U, Hiddemann W, Buske C, Bohlander SK