microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival
microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival
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DOI：
10.1182/blood-2010-01-263889
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发表时间：
2010-08-12
期刊：
影响因子：
20.3
通讯作者：
Calin, George A.
中科院分区：
文献类型：
--
作者：
Rossi, Simona;Shimizu, Masayoshi;Calin, George A.
microRNAs（miRNAs）的异常表达与慢性淋巴细胞白血病（CLL）患者的临床结局相关。为了确定一个强大的和易于评估的预后和生存的miRNA生物标志物，我们进行了定量逆转录聚合酶链反应（qRT-PCR）分析104例CLL患者明确的染色体17 p状态，我们验证了我们的研究结果与miRNA微阵列数据从一个独立的队列80例患者。我们发现miR-15 a、miR-21、miR-34 a、miR-155和miR-181 b在染色体17 p缺失的CLL与正常17 p和正常核型的CLL之间差异表达，并且miR-181 b在治疗难治性病例中下调。miR-21表达水平在预后不良和预测总生存期（OS）的患者中显著较高，miR-181 b表达水平显著预测无治疗生存期。我们开发了21 FK评分（miR-21 qRT-PCR，荧光原位杂交，核型），根据OS对患者进行分层，发现评分低的患者OS时间显著延长。当我们评估21 FK评分与最常用的预后因素的相对功效时，该评分在两个CLL队列中最显著。我们的结论是，21 FK评分代表了一个有用的工具，用于区分预后良好和预后不良的CLL患者。（血。2010;116（6）：945-952）
Aberrant expression of microRNAs (miRNAs) has been associated with clinical outcome in patients with chronic lymphocytic leukemia (CLL). To identify a powerful and easily assessable miRNA bio-marker of prognosis and survival, we performed quantitative reverse-transcription polymerase chain reaction (qRT-PCR) profiling in 104 CLL patients with a well-defined chromosome 17p status, and we validated our findings with miRNA microarray data from an independent cohort of 80 patients. We found that miR-15a, miR-21, miR-34a, miR-155, and miR-181b were differentially expressed between CLLs with chromosome 17p deletion and CLLs with normal 17p and normal karyotype, and that miR-181b was down-regulated in therapy-refractory cases. miR-21 expression levels were significantly higher in patients with poor prognosis and predicted overall survival (OS), and miR-181b expression levels significantly predicted treatment-free survival. We developed a 21FK score (miR-21 qRT-PCR, fluorescence in situ hybridization, Karyotype) to stratify patients according to OS and found that patients with a low score had a significantly longer OS time. When we evaluated the relative power of the 21FK score with the most used prognostic factors, the score was the most significant in both CLL cohorts. We conclude that the 21FK score represents a useful tool for distinguishing between good-prognosis and poor-prognosis CLL patients. (Blood. 2010;116(6):945-952)