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

Deregulation of microRNA involved in hematopoiesis and the immune response in HTLV-I adult T-cell leukemia
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DOI:
10.1182/blood-2008-11-189845
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发表时间:
2009-05-14
期刊:
影响因子:
20.3
通讯作者:
Nicot, Christophe
Nicot, Christophe
中科院分区:
医学1区
文献类型:
--
作者:
Bellon, Marcia;Lepelletier, Yves;Nicot, Christophe

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人类T细胞白血病病毒I型(HTLV-I)是成人T细胞白血病(ATL)的病原体,ATL是一种侵袭性淋巴组织增生性疾病。microRNA(miRNAs)在造血干细胞祖细胞(HSCP)的造血和谱系定型过程中差异表达。在此,我们报告了造血特异性miR-223、miR-181 a、miR-150、miR-142.3p和miR-155在体外HTLV-I感染的细胞和未培养的离体ATL细胞中的异常表达。我们的研究结果表明,HTLV-I感染的细胞具有有利于T细胞分化的miRNA的不平衡表达。我们还发现了以前被认为是先天免疫调节因子的miRNA的表达改变:miR-155,miR-125 a,miR-132和miR-146。引人注目的是,我们的数据还揭示了离体ATL肿瘤细胞和体外HTLV-1细胞系之间的显著差异。具体而言,miR-150和miR-223在ATL患者中上调,但在HTLV-I细胞系中一致下调,表明ATL细胞和体外建立的细胞来源于不同的细胞群体。(血。2009;113:4914-4917)
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. (Blood. 2009;113:4914-4917)