Expression of ribosomal and translation-associated genes is correlated with a favorable clinical course in chronic lymphocytic leukemia.
B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous 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.
Dürig
Jan
J
Department of Hematology, Medical Faculty, University of Essen, Germany. duerig@t-online.de
Nückel
Holger
H
Hüttmann
Andreas
A
Kruse
Elisabeth
E
Hölter
Tanja
T
Halfmeyer
Katja
K
Führer
Anja
A
Rudolph
Roland
R
Kalhori
Naser
N
Nusch
Arnd
A
Deaglio
Silvia
S
Malavasi
Fabio
F
Möröy
Tarik
T
Klein-Hitpass
Ludger
L
Dührsen
Ulrich
U
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000368:Aged; D015703:Antigens, CD; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011379:Prognosis; D014176:Protein Biosynthesis / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics*; D012307:Risk Factors; D016896:Treatment Outcome
D015703:Antigens, CD; D008562:Membrane Glycoproteins; D012269:Ribosomal Proteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1