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Genes that influence the development of adult T-cell leukemia

影响成人 T 细胞白血病发展的基因

基本信息

批准号：
10670414
负责人：
HASEGAWA Hitoshi
金额：
$ 2.37万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670414/
关键词：
Adult T-cell leukemia Tyrosine kinase Chemokines CD151 Adult T-cell leu kemia Adult T cell leukemia HTLV-1 tyrosine Kinase

项目摘要

The molecular mechanisms that influence the clinical development of adult T cell leukemia (ATL) are not fully understood. In the present study, we tried to identify the mRNA species that are differentially expressed in fresh peripheral blood mononuclear cells from patients with acute ATL and normal subjects, and MOLT-4. The ten genes ; tyrosine kinase Pyk2, JAK3, Tyk, Typo, HYL, Z225, MIP-lalpha, CD151, CCR7/EBI1, and CD70, were amplified preferentially in samples of PBMC from patients with acute ATL.Among these 10 genes, we further analyzed the role of CCR7/EBI1, Pyk2, and CD151 in pathogenesis of ATL.First, ATL cells from patients with lymphoid organ involvement expressed significantly more CCR7/EBI1 than normal T cells and ATL cells from patients without lymphoid organ involvement. This suggests that increased CCR7EBI1 expression plays a role in lymphoid organ infiltration of ATL cells. Second, Pyk2 was expressed higher in 6 freshly isolated ATL cells than in PBMC of normal subjects and MOLT-4. The Pyk2-transfected SF-HT clones grew without IL-2, while control vector-transfected SF-HT cells did not grow. Therefore, these findings suggest that Pyk2 may play a role on the progression of ATL through T cell activation. Finally, the expression levels of CD151, α4β1 integrin, andα5β1 integrin on ATL cells from lymph nodes of lymphoma-type ATL patients were significantly higher than those on circulating ATL cells from leukemia-type ATL patients. This suggests that the increased expression of these integrins may contribute to lymphoma formation.

影响成人T细胞白血病(ATL)临床发展的分子机制尚不完全清楚。在本研究中，我们试图确定在急性ATL患者和正常人以及MOLT-4新鲜外周血单个核细胞中差异表达的mRNA种类。从急性ATL患者的PBMC中优先扩增出酪氨酸激酶PYK2、JAK3、Tyk、Typo、HYL、Z225、MIP-α、CD151、CCR7/EBI1和CD70等10个基因，进一步分析了CCR7/EBI1、PYK2和CD151在ATL发病中的作用。提示CCR7EBI1的高表达在ATL细胞的淋巴器官浸润中起一定作用。第二，在6个新鲜分离的ATL细胞中，Pyk2的表达高于正常人和MOLT-4的PBMC。PYK2基因转染的SF-HT克隆在没有IL-2的情况下生长，而对照载体转染的SF-HT细胞不生长。因此，这些发现提示，Pyk2可能通过T细胞活化在ATL的进展中发挥作用。CD151、α4β1整合素和α5β1整合素在淋巴瘤型ATL患者淋巴组织中的表达水平显著高于白血病患者外周血中的ATL细胞。这表明，这些整合素的表达增加可能有助于淋巴瘤的形成。