microRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma
microRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma
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DOI：
10.1182/blood-2012-08-447375
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发表时间：
2013-09-19
期刊：
影响因子：
20.3
通讯作者：
Chan, Wing C.
中科院分区：
文献类型：
--
作者：
Liu, Cuiling;Iqbal, Javeed;Chan, Wing C.
间变性大细胞淋巴瘤(ALCL)至少包括两种全身性疾病，通过间变性淋巴瘤激酶(ALK)的表达或不表达来区分。我们对33例ALK阳性(ALK[1])ALCL、25例ALK阴性(ALK[2])ALCL、9例血管免疫母细胞性T细胞淋巴瘤、11例非特异性外周T细胞淋巴瘤(PTCLNOS)和正常T细胞进行了全基因组microRNA(MiRNA)谱分析，结果表明，除miR-146a外，ALCL表达许多在正常T细胞中高表达的miRNAs。非监督系统聚类法显示ALCL、PTCL-NOS和PTCL的AITL亚型有明显的聚集性。在非监督分析中，ALK(1)ALCL和ALK(-)ALCL的病例被穿插，提示在分子水平上有密切的关系。我们发现了7个miRNAs的miRNA特征(5个上调：miR-512-3p、miR-886-5p、miR-886-3p、miR-708、miR-135b；2个下调：miR-146a、miR-155)与ALK(1)ALCL病例显著相关。此外，我们还获得了一个11-miRNA信号(4上调：miR-210、miR-197、miR-191、miR-512-3p；7下调：miR-451、miR-146a、miR-22、miR-455-3p、miR-455-5p、miR-143、miR-494)，以区别于其他PTCL。我们的体外研究发现了一组与ALK表达相关的32个miRNAs。其中，与92簇相似的iR-17及其类似物也在ALK(1)ALCL中高表达，可能是ALK致癌途径的重要下游效应分子。
Anaplastic large-cell lymphomas (ALCLs) encompass at least 2 systemic diseases distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. We performed genome-wide microRNA (miRNA) profiling on 33 ALK-positive (ALK[1]) ALCLs, 25 ALK-negative (ALK[2]) ALCLs, 9 angioimmunoblastic T-cell lymphomas, 11 peripheral T-cell lymphomas not otherwise specified (PTCLNOS), and normal T cells, and demonstrated that ALCLs express many of the miRNAs that are highly expressed in normal T cells with the prominent exception of miR-146a. Unsupervised hierarchical clustering demonstrated distinct clustering of ALCL, PTCL-NOS, and the AITL subtype of PTCL. Cases of ALK(1) ALCL and ALK(-) ALCL were interspersed in unsupervised analysis, suggesting a close relationship at the molecular level. We identified an miRNA signature of 7 miRNAs (5 upregulated: miR-512-3p, miR-886-5p, miR-886-3p, miR-708, miR-135b; 2 downregulated: miR-146a, miR-155) significantly associated with ALK(1) ALCL cases. In addition, we derived an 11-miRNA signature (4 upregulated: miR-210, miR-197, miR-191, miR-512-3p; 7 downregulated: miR-451, miR-146a, miR-22, miR-455-3p, miR-455-5p, miR-143, miR-494) that differentiates ALK(-) ALCL from other PTCLs. Our in vitro studies identified a set of 32 miRNAs associated with ALK expression. Of these, themiR-17 similar to 92 cluster and its paralogues were also highly expressed in ALK(1) ALCL and may represent important downstream effectors of the ALK oncogenic pathway.