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人嗜T淋巴细胞病毒I型成人T细胞白血病中参与造血和免疫反应的微小RNA失调

Deregulation of microRNA involved in hematopoiesis and the immune response in HTLV-I adult T-cell leukemia.

作者信息

Bellon Marcia, Lepelletier Yves, Hermine Olivier, Nicot Christophe

机构信息

University of Kansas Medical Center, Department of Pathology and Laboratory Medicine, Center for Viral Oncology and University of Kansas Cancer Center, Kansas City, 66160, USA.

出版信息

Blood. 2009 May 14;113(20):4914-7. doi: 10.1182/blood-2008-11-189845. Epub 2009 Feb 26.

Abstract

Human T-cell leukemia virus type-I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL), an aggressive lymphoproliferative disease. MicroRNAs (miRNAs) are differentially expressed during hematopoiesis and lineage commitment of hematopoietic stem cell progenitors (HSCPs). Here, we report aberrant expression of hematopoietic-specific miR-223, miR-181a, miR-150, miR-142.3p, and miR-155 in HTLV-I-infected cells in vitro and uncultured ex vivo ATL cells. Our results suggest that HTLV-I-infected cells have an unbalanced expression of miRNA that favors T-cell differentiation. We also found altered expression of miRNA previously recognized as innate immunity regulators: miR-155, miR-125a, miR-132, and miR-146. Strikingly, our data also revealed significant differences between ex vivo ATL tumor cells and in vitro HTLV-I cell lines. Specifically, miR-150 and miR-223 were up-regulated in ATL patients but consistently down-regulated in HTLV-I cell lines, suggesting that ATL cells and in vitro-established cells are derived from distinct cellular populations.

摘要

人类I型T细胞白血病病毒(HTLV-I)是成人T细胞白血病(ATL)的病原体,ATL是一种侵袭性淋巴细胞增殖性疾病。微小RNA(miRNA)在造血过程以及造血干细胞祖细胞(HSCP)的谱系定向过程中表达存在差异。在此,我们报告了造血特异性miR-223、miR-181a、miR-150、miR-142.3p和miR-155在体外HTLV-I感染细胞以及未经培养的体外ATL细胞中的异常表达。我们的结果表明,HTLV-I感染细胞中miRNA的表达失衡,有利于T细胞分化。我们还发现先前被认为是先天免疫调节因子的miRNA表达发生了改变:miR-155、miR-125a、miR-132和miR-146。引人注目的是,我们的数据还揭示了体外ATL肿瘤细胞与体外HTLV-I细胞系之间存在显著差异。具体而言,miR-150和miR-223在ATL患者中上调,但在HTLV-I细胞系中持续下调,这表明ATL细胞和体外建立的细胞源自不同的细胞群体。

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