Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia.

Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia.
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DOI:
10.1371/journal.pone.0002141
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发表时间:
2008-05-14
期刊:
影响因子:
3.7
通讯作者:
Debernardi S
Debernardi S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dixon-McIver A;East P;Mein CA;Cazier JB;Molloy G;Chaplin T;Andrew Lister T;Young BD;Debernardi S

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急性髓性白血病(AML)是成人中最常见的急性白血病;然而,该疾病的遗传病因尚未完全了解。对100例AML患者进行了157种成熟miRNA的定量表达谱分析,这些患者代表了AML中常见的已知核型谱。本文报道的主要观察结果是,携带t(15; 17)易位的AML在整个基因组中具有独特的特征,包括位于人类14q32印迹结构域中的miRNA子集的上调。该组包括miR-127、miR-154、miR-154 *、miR-299、miR-323、miR-368和miR-370。此外,鉴定了特定的miRNA子集,其提供了AML中主要易位介导的基因融合事件的分子特征。方差分析显示,相对于来自健康供体的骨髓,白血病组中33种miRNA的显著失调。使用miRNA特异性锁核酸(LNA)探针对冷冻保存的患者细胞进行荧光原位杂交分析,证实了通过实时PCR获得的结果。这项研究是在桑格数据库(www.example.com)中报道的大约五分之一的miRNA上进行的,证明了使用miRNA表达对癌症进行亚分类的潜力,并表明了在白血病病因学中的作用。
Acute myeloid leukaemia (AML) is the most common acute leukaemia in adults; however, the genetic aetiology of the disease is not yet fully understood. A quantitative expression profile analysis of 157 mature miRNAs was performed on 100 AML patients representing the spectrum of known karyotypes common in AML. The principle observation reported here is that AMLs bearing a t(15;17) translocation had a distinctive signature throughout the whole set of genes, including the up regulation of a subset of miRNAs located in the human 14q32 imprinted domain. The set included miR-127, miR-154, miR-154*, miR-299, miR-323, miR-368, and miR-370. Furthermore, specific subsets of miRNAs were identified that provided molecular signatures characteristic of the major translocation-mediated gene fusion events in AML. Analysis of variance showed the significant deregulation of 33 miRNAs across the leukaemic set with respect to bone marrow from healthy donors. Fluorescent in situ hybridisation analysis using miRNA-specific locked nucleic acid (LNA) probes on cryopreserved patient cells confirmed the results obtained by real-time PCR. This study, conducted on about a fifth of the miRNAs currently reported in the Sanger database (microrna.sanger.ac.uk), demonstrates the potential for using miRNA expression to sub-classify cancer and suggests a role in the aetiology of leukaemia.
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