Downregulated Dicer expression predicts poor prognosis in chronic lymphocytic leukemia
Downregulated Dicer expression predicts poor prognosis in chronic lymphocytic leukemia
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DOI：
10.1111/j.1349-7006.2012.02234.x
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发表时间：
2012-05
期刊：
影响因子：
5.7
通讯作者：
Dan-xia Zhu;L. Fan;R. Lu;Cheng Fang;Wenyi Shen;Zhi-jian Zou;Yin-Hua Wang;Hua-yuan Zhu;K. Miao;P. Liu;W. Xu;Jian-yong Li
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文献类型：
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作者：
Dan-xia Zhu;L. Fan;R. Lu;Cheng Fang;Wenyi Shen;Zhi-jian Zou;Yin-Hua Wang;Hua-yuan Zhu;K. Miao;P. Liu;W. Xu;Jian-yong Li
慢性淋巴细胞白血病（CLL）是西方世界最常见的白血病。已经提出微小RNA（miRNA）表达的改变在CLL发病机制中起作用。Dicer和Drosha是miRNA生物发生的主要调节因子，其表达的失调已被指示为在各种癌症中观察到的miRNA改变的可能原因。为了研究Dicer和Drosha在CLL中的作用，我们使用真实的时间聚合酶链反应方法评估了165例CLL患者中Dicer和Drosha的表达及其与其他预后因素的相关性，包括Binet分期、免疫球蛋白重链可变基因（IGHV）突变状态、TP 53突变状态、ZAP-70蛋白和CD 38表达水平。IGHV基因未突变患者的Dicer表达显著低于IGHV突变患者。Dicer的低表达水平也与CD 38和ZAP-70的高水平以及更具侵袭性的Binet分期显著相关。我们还分析了Dicer在不同细胞遗传学亚组中的表达。Dicer水平在不良细胞遗传学异常（17 p13或11q22.3缺失）患者中较低，而在良好风险细胞遗传学异常（13 q14缺失为唯一异常）患者中较高。此外，CLL中Dicer的较低表达显示与较短的总生存期（OS）（P = 0.0046）以及与降低的无治疗生存期（TFS）（P = 0.0006）强相关。相比之下，在这些患者组中没有观察到Drosha表达的差异。我们的数据表明，Dicer表达可能在CLL的进展和预后中发挥重要作用。（Cancer Sci 2012; 103：875-881）
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Alterations in microRNAs (miRNAs) expression have been proposed to play a role in CLL pathogenesis. Dicer and Drosha are the main regulators of miRNA biogenesis, and deregulation of their expression has been indicated as a possible cause of miRNA alterations observed in various cancers. To investigate the role of Dicer and Drosha in CLL, we assessed the expression of Dicer and Drosha and their correlation with other prognostic factors, including Binet stages, immunoglobulin heavy chain variable gene (IGHV) mutation status, TP53 mutation status, ZAP‐70 protein and CD38 expression level in 165 CLL patients by using real‐time polymerase chain reaction methods. Patients with unmutated IGHV genes had significantly lower expression of Dicer than patients with IGHV mutations. The lower expression level of Dicer was also significantly associated with higher level of CD38 and ZAP‐70, and more aggressive Binet stage. We also analyzed Dicer expression in different cytogenetic subgroups. Lower Dicer level was found in patients with unfavorable cytogenetic aberrations (deletion in 17p13 or 11q22.3) in contrast to higher level in good risk cytogenetics (deletion in 13q14 as the sole abnormality). Furthermore, the lower expression of Dicer in CLL shows a strong association with shorter overall survival (OS) (P = 0.0046) as well as with reduced treatment free survival (TFS) (P = 0.0006). By contrast, no differences in the expression of Drosha among these groups of patients were observed. Our data suggest that Dicer expression may play an important role in the progression and prognosis of CLL. (Cancer Sci 2012; 103: 875–881)