A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia
A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia
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DOI：
10.1056/nejmoa050995
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发表时间：
2005-10-27
影响因子：
158.5
通讯作者：
Croce, CM
中科院分区：
文献类型：
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作者：
Calin, GA;Ferracin, M;Croce, CM
背景：microRNA表达谱可用于区分慢性淋巴细胞白血病(CLL)患者的正常B细胞和恶性B细胞。方法：我们对94例已知70-kD Zeta相关蛋白(ZAP-70)表达水平、重排免疫球蛋白重链可变区(IGV(SubH))基因突变状态以及从诊断到首次治疗时间已知的CLL细胞的microRNA表达谱进行了研究。结果：一个独特的microRNA表达谱由13个基因组成(在190个基因分析中)，区分了低水平表达ZAP-70的CLL和高水平表达的病例，以及未突变的IGV(SubH)和突变的IGV(SubH)。同样的microRNA特征也与疾病进展的存在或不存在有关。我们还在miR-16-1-miR-15a初级前体中发现了一个胚系突变，该突变导致了体内和体外microRNA的低水平表达，并与正常等位基因的缺失有关。在75例慢性淋巴细胞性白血病患者中，11例测序的42个microRNA中有5个发生胚系或体细胞突变，而在160例非癌对照中未发现此类突变(P
BACKGROUND:MicroRNA expression profiles can be used to distinguish normal B cells from malignant B cells in patients with chronic lymphocytic leukemia (CLL). We investigated whether microRNA profiles are associated with known prognostic factors in CLL.METHODS:We evaluated the microRNA expression profiles of 94 samples of CLL cells for which the level of expression of 70-kD zeta-associated protein (ZAP-70), the mutational status of the rearranged immunoglobulin heavy-chain variable-region (IgV(sub H)) gene, and the time from diagnosis to initial treatment were known. We also investigated the genomic sequence of 42 microRNA genes to identify abnormalities.RESULTS:A unique microRNA expression signature composed of 13 genes (of 190 analyzed) differentiated cases of CLL with low levels of ZAP-70 expression from those with high levels and cases with unmutated IgV(sub H) from those with mutated IgV(sub H). The same microRNA signature was also associated with the presence or absence of disease progression. We also identified a germ-line mutation in the miR-16-1-miR-15a primary precursor, which caused low levels of microRNA expression in vitro and in vivo and was associated with deletion of the normal allele. Germ-line or somatic mutations were found in 5 of 42 sequenced microRNAs in 11 of 75 patients with CLL, but no such mutations were found in 160 subjects without cancer (P