Reduced level of the BCL11B protein is associated with adult T-cell leukemia/lymphoma.

Reduced level of the BCL11B protein is associated with adult T-cell leukemia/lymphoma.
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DOI:
10.1371/journal.pone.0055147
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Isobe M
Isobe M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kurosawa N;Fujimoto R;Ozawa T;Itoyama T;Sadamori N;Isobe M

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成人T细胞白血病/淋巴瘤(ATLL)在一小部分人T细胞白血病病毒I型(HTLV-I)感染的个体中发生。然而,HTLV-I引起ATLL的机制尚未完全阐明。为了提供白血病发生的多步骤过程的基本见解,我们绘制了50例ATLL病例的染色体异常,以确定ATLL的潜在关键调节因子。在一个ATLL的情况下,与易位t(14;17)(q32;q22-23)的断点分析,导致Kruppel锌指基因,BCL 11 B,这在T细胞发育中起着至关重要的作用的鉴定。在我们通过免疫荧光分析检查的7例ATLL中,4例显示低BCL 11B信号强度,1例显示中等BCL 11B信号强度。在HTLV-I阳性T细胞系中也发现了BCL 11B蛋白水平的显著降低。BCL 11B的异位表达导致ATLL衍生的细胞系中显著的生长抑制,但在Jurkat细胞中不显著。我们的遗传和功能数据提供了第一个证据,表明BCL 11B蛋白水平的降低是ATLL白血病发生多步骤进展的关键事件。
Adult T-cell leukemia/lymphoma (ATLL) develops in a small proportion of human T-cell leukemia virus type I (HTLV-I)-infected individuals. However, the mechanism by which HTLV-I causes ATLL has not been fully elucidated. To provide fundamental insights into the multistep process of leukemogenesis, we have mapped the chromosomal abnormalities in 50 ATLL cases to identify potential key regulators of ATLL. The analysis of breakpoints in one ATLL case with the translocations t(14;17)(q32;q22-23) resulted in the identification of a Kruppel zinc finger gene, BCL11B, which plays a crucial role in T-cell development. Among the 7 ATLL cases that we examined by immunofluorescence analysis, 4 displayed low and one displayed moderate BCL11B signal intensities. A dramatically reduced level of the BCL11B protein was also found in HTLV-I-positive T-cell lines. The ectopic expression of BCL11B resulted in significant growth suppression in ATLL-derived cell lines but not in Jurkat cells. Our genetic and functional data provide the first evidence that a reduction in the level of the BCL11B protein is a key event in the multistep progression of ATLL leukemogenesis.
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