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Prepublished online as a Blood First Edition Paper on November 27, 2002; DOI 10.1182/blood-2002-09-2683.
Submitted September 5, 2002
Accepted November 1, 2002
Expression of ribosomal and translation-associated genes is correlated with a favorable clinical course in chronic lymphocytic leukemia
Jan Duerig*, Holger Nueckel, Andreas Huettmann, Elisabeth Kruse, Tanja Hoelter, Katja Halfmeyer, Anja Fuehrer, Roland Rudolph, Naser Kalhori, Arnd Nusch, Silvia Deaglio, Fabio Malavasi, Tarik Moeroey, Ludger Klein-Hitpass, and Ulrich Duehrsen
Hematology, University Hospital Essen, Essen, NRW, Germany
Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, NRW, Germany
Gemeinschaftspraxis fuer Haematologie und Onkologie Essen, Essen, NRW, Germany
Gemeinschaftspraxis fuer Haematologie und Onkologie Velbert, Essen, NRW, Germany
Department of Genetics, Biology and Biochemistry, University of Torino, Torino, Italy
Institute of Cell Biology, University Hospital Essen, Essen, NRW, Germany
* Corresponding author; email: duerig{at}t-online.de.
B-cell chronic lymphocytic leukemia (B-CLL) is a heterogenous disease with a highly variable clinical course. Recent studies have shown that CD38 surface expression on the malignant cell clone may serve as a prognostic marker in that CD38 positive B-CLL patients are characterized by a more advanced disease stage, lesser responsiveness to chemotherapy and shorter survival than CD38 negative cases. To further investigate the molecular phenotype of these two clinical subgroups, we compared the gene expression profiles of CD38 positive (N=25) with CD38 negative (N=45) B-CLL cases using oligonucleotide-based DNA chip microarrays representative of ~5600 genes. The results show that B-CLLs display a common gene expression profile that is largely independent of CD38 expression. Nonetheless, the expression of 15 genes differed significantly between the two groups, including genes that are involved in the regulation of cell survival.
Furthermore, unsupervised hierarchical cluster analysis of 76 B-CLL samples led to the separation of two major subgroups, comprising 20 and 56 patients, respectively. Clustering to the smaller group was due in part to the coordinate high expression of a large number of ribosomal and other translation-associated genes including elongation factors. Importantly, we found that patients with a high expression of translation factors were characterized by a more favorable clinical course with significantly longer progression free survival and lesser chemotherapy requirements as compared to the remaining patients (p<0.05). Our data show that gene expression profiling can help identify B-CLL subtypes with different clinical characteristics. Furthermore, our results suggest a role of translation-associated genes in the pathogenesis of B-CLL.
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