MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias
MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias
复制标题
DOI：
10.1073/pnas.0404432101
复制
发表时间：
2004-08-10
影响因子：
11.1
通讯作者：
Croce, CM
中科院分区：
文献类型：
--
作者：
Calin, GA;Liu, CG;Croce, CM
尽管微小RNA（miRNAs）在发育过程中对基因表达的调控起着重要作用这一点日益明确[安布罗斯，V.（2003年）《细胞》113卷，673 - 676页；麦克马纳斯，M.T.（2003年）《癌症生物学研讨》13卷，253 - 258页]，但对于miRNAs在正常细胞和肿瘤细胞中的表达水平或功能却知之甚少。我们现在利用一种包含数百种人类前体和成熟miRNA寡核苷酸探针的微阵列，报告了人类B细胞慢性淋巴细胞白血病（CLL）中miRNAs的全基因组表达谱。这种方法使我们能够识别CLL样本和正常CD5⁺B细胞之间miRNome表达的显著差异；数据通过Northern杂交分析和实时逆转录聚合酶链反应（RT - PCR）得到了证实。至少可以识别出两个不同的CLL样本群，它们与Zap - 70表达的有无相关，Zap - 70是疾病早期进展的一个预测因子。两种miRNA特征分别与表达的免疫球蛋白可变区基因是否存在突变或13q14缺失相关。这些数据表明，miRNA表达模式与这种白血病的生物学和临床行为有关。
Little is known about the expression levels or function of microRNAs (miRNAs) in normal and neoplastic cells, although it is becoming clear that miRNAs play important roles in the regulation of gene expression during development [Ambros, V. (2003) Cell 113, 673-676; McManus, M. T. (2003) Semin. Cancer Biol. 13, 253-258]. We now report the genomewide expression profiling of miRNAs in human B cell chronic lymphocytic leukemia (CLL) by using a microarray containing hundreds of human precursor and mature miRNA oligonucleotide probes. This approach allowed us to identify significant differences in miRNome expression between CLL samples and normal CD5+ B cells; data were confirmed by Northern blot analyses and real-time RT-PCR. At least two distinct clusters of CLL samples can be identified that were associated with the presence or absence of Zap-70 expression, a predictor of early disease progression. Two miRNA signatures were associated with the presence or absence of mutations in the expressed Ig variable-region genes or with deletions at 13q14, respectively. These data suggest that miRNA expression patterns have relevance to the biological and clinical behavior of this leukemia.