Visone Rosa, Rassenti Laura Z, Veronese Angelo, Taccioli Cristian, Costinean Stefan, Aguda Baltazar D, Volinia Stefano, Ferracin Manuela, Palatini Jeff, Balatti Veronica, Alder Hansjuerg, Negrini Massimo, Kipps Thomas J, Croce Carlo M
Department of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Blood. 2009 Oct 29;114(18):3872-9. doi: 10.1182/blood-2009-06-229211. Epub 2009 Aug 28.
Chromosomal abnormalities, immunoglobulin heavy chain variable-region (IGHV) gene mutation status, and zeta-associated protein 70 (ZAP-70) expression levels have independent prognostic relevance in chronic lymphocytic leukemia (CLL); however, their concordance is variable. Because deregulation of microRNAs has been linked to disease initiation and progression in CLL, we studied the value of the microRNAs as a signature for CLL patients with specific chromosomal abnormalities. We identified 32 microRNAs able to discriminate the 11q deletion, 17p deletion, trisomy 12, 13q deletion, and normal karyotype cytogenetic subgroups. The expression values of 9 among the 32 microRNAs (miR-151-3p, miR-34a, miR-29c, miR-29b, miR-155, miR-148a, miR-146a, miR-146b5p, and miR-640) were correlated with gene expression data from the same samples to assess their biologic impact on CLL. In this study we also found that IGHV unmutated, high expression of ZAP-70 protein, and low expression of the miR-223, miR-29c, miR-29b, and miR-181 family were strongly associated with disease progression in CLL cases harboring 17p deletion, whereas in those harboring trisomy 12 only high expression of the miR-181a, among the analyzed parameters, suggested more aggressive disease. Thus, the use of the microRNA-based classifications may yield clinically useful biomarkers of tumor behavior in CLL.
染色体异常、免疫球蛋白重链可变区（IGHV）基因突变状态以及ζ相关蛋白70（ZAP-70）表达水平在慢性淋巴细胞白血病（CLL）中具有独立的预后相关性；然而，它们之间的一致性是可变的。由于微小RNA的失调与CLL的疾病发生和进展有关，我们研究了微小RNA作为具有特定染色体异常的CLL患者标志物的价值。我们鉴定出32种微小RNA能够区分11q缺失、17p缺失、三体12、13q缺失和正常核型细胞遗传学亚组。32种微小RNA中的9种（miR-151-3p、miR-34a、miR-29c、miR-29b、miR-155、miR-148a、miR-146a、miR-146b5p和miR-640）的表达值与来自相同样本的基因表达数据相关，以评估它们对CLL的生物学影响。在本研究中，我们还发现，在伴有17p缺失的CLL病例中，IGHV未突变、ZAP-70蛋白高表达以及miR-223、miR-29c、miR-29b和miR-181家族低表达与疾病进展密切相关，而在伴有三体12的病例中，在所分析的参数中，只有miR-181a高表达提示疾病更具侵袭性。因此，基于微小RNA的分类可能产生CLL中肿瘤行为的临床有用生物标志物。
