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Prepublished online as a Blood First Edition Paper on November 27, 2002; DOI 10.1182/blood-2002-09-2683.
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Blood, 1 April 2003, Vol. 101, No. 7, pp. 2748-2755
NEOPLASIA
Expression of ribosomal and translation-associated genes is
correlated with a favorable clinical course in chronic lymphocytic
leukemia
Jan Dürig,
Holger Nückel,
Andreas Hüttmann,
Elisabeth Kruse,
Tanja Hölter,
Katja Halfmeyer,
Anja Führer,
Roland Rudolph,
Naser Kalhori,
Arnd Nusch,
Silvia Deaglio,
Fabio Malavasi,
Tarik Möröy,
Ludger Klein-Hitpass, and
Ulrich Dührsen
From the Department of Hematology, the Institute for
Medical Informatics, Biometry and Epidemiology, and the Institute of
Cell Biology, Medical Faculty, University of Essen; Gemeinschaftspraxis
für Hämatologie und Onkologie Essen; Gemeinschaftspraxis
für Hämatologie und Onkologie Velbert,
Germany; and the Laboratory of Immunogenetics, Department
of Genetics, Biology and Biochemistry, University of Torino,
Italy.
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+ patients with
B-CLL are characterized by advanced disease stage, lesser
responsiveness to chemotherapy, and shorter survival than CD38 patients. To further investigate the molecular
phenotype of these 2 clinical subgroups, we compared the gene
expression profiles of CD38+ (n = 25) with
CD38 (n = 45) B-CLL patients using
oligonucleotide-based DNA chip microarrays representative of
approximately 5600 genes. The results showed that B-CLLs display a
common gene expression profile that is largely independent of CD38
expression. Nonetheless, the expression of 14 genes differed
significantly between the 2 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 2 major subgroups, comprising 20 and 56 patients. 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
high expression of translation factors were characterized by a more
favorable clinical course with significantly longer progression-free
survival and reduced chemotherapy requirements than the remaining
patients (P < .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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