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 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 translationassociated genes in the pathogenesis of

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Expression profiling reveals a distinct transcription signature in follicular thyroid carcinomas with a PAX8-PPARγ fusion oncogene

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Transgelin is a marker of repopulating mesangial cells after injury and promotes their proliferation and migration

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