Dürig Jan, Nückel Holger, Hüttmann Andreas, Kruse Elisabeth, Hölter Tanja, Halfmeyer Katja, Führer Anja, Rudolph Roland, Kalhori Naser, Nusch Arnd, Deaglio Silvia, Malavasi Fabio, Möröy Tarik, Klein-Hitpass Ludger, Dührsen Ulrich
Department of Hematology, Medical Faculty, University of Essen, Germany.
Blood. 2003 Apr 1;101(7):2748-55. doi: 10.1182/blood-2002-09-2683. Epub 2002 Nov 27.
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.
B细胞慢性淋巴细胞白血病（B-CLL）是一种临床病程高度可变的异质性疾病。最近的研究表明，恶性细胞克隆表面的CD38表达可能作为一种预后标志物，因为与CD38（-）的B-CLL患者相比，CD38（+）的B-CLL患者具有疾病分期晚、对化疗反应性差和生存期短的特点。为了进一步研究这两个临床亚组的分子表型，我们使用代表约5600个基因的基于寡核苷酸的DNA芯片微阵列，比较了25例CD38（+）和45例CD38（-）的B-CLL患者的基因表达谱。结果显示，B-CLL呈现出一种基本独立于CD38表达的共同基因表达谱。尽管如此，两组之间14个基因的表达存在显著差异，包括参与细胞存活调节的基因。此外，对76例B-CLL样本进行的无监督层次聚类分析产生了两个主要亚组，分别包含20例和56例患者。聚类到较小亚组部分归因于大量核糖体及其他与翻译相关基因（包括延伸因子）的协同高表达。重要的是，我们发现翻译因子高表达的患者具有更有利的临床病程，与其余患者相比，无进展生存期显著更长，化疗需求减少（P<.05）。我们的数据表明，基因表达谱分析有助于识别具有不同临床特征的B-CLL亚型。此外，我们的结果提示了与翻译相关的基因在B-CLL发病机制中的作用。
