title: Expression of ribosomal and translation-associated genes is correlated with a favorable clinical course in chronic lymphocytic leukemia.
abstract: 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.
authors.affiliation: Department of Hematology, Medical Faculty, University of Essen, Germany. duerig@t-online.de
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
authors.forename: Holger
authors.initials: H
authors.lastname: Nückel
authors.forename: Andreas
authors.initials: A
authors.lastname: Hüttmann
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kruse
authors.forename: Tanja
authors.initials: T
authors.lastname: Hölter
authors.forename: Katja
authors.initials: K
authors.lastname: Halfmeyer
authors.forename: Anja
authors.initials: A
authors.lastname: Führer
authors.forename: Roland
authors.initials: R
authors.lastname: Rudolph
authors.forename: Naser
authors.initials: N
authors.lastname: Kalhori
authors.forename: Arnd
authors.initials: A
authors.lastname: Nusch
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
authors.forename: Tarik
authors.initials: T
authors.lastname: Möröy
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein-Hitpass
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dührsen
mesh_terms: 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
chemical_list: D015703:Antigens, CD; D008562:Membrane Glycoproteins; D012269:Ribosomal Proteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1