Genes that influence the development of adult T-cell leukemia

影响成人T细胞白血病（ATL）临床发展的分子机制尚未完全了解。在本研究中，我们试图确定的mRNA种类，差异表达的新鲜外周血单核细胞从急性ATL患者和正常人，和MOLT-4。十个基因;酪氨酸激酶Pyk 2、JAK 3、Tyk、Typo、HYL、Z225、MIP-1 α、CD 151、CCR 7/EBI 1和CD 70在急性ATL患者PBMC样品中优先扩增。在这10个基因中，我们进一步分析了CCR 7/EBI 1、Pyk 2和CD 151在ATL发病机制中的作用。来自淋巴器官受累患者的ATL细胞表达的CCR 7/EBI 1显著高于正常T细胞和来自无淋巴器官受累患者的ATL细胞。这表明增加的CCR 7 EBI 1表达在ATL细胞的淋巴器官浸润中起作用。第二，Pyk 2在6个新鲜分离的ATL细胞中的表达高于正常受试者和MOLT-4的PBMC。Pyk 2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，这些发现表明Pyk 2可能通过T细胞活化在ATL的进展中发挥作用。最后，来自淋巴瘤型ATL患者的淋巴结的ATL细胞上的CD 151、α4β1整合素和α5β1整合素的表达水平显著高于来自白血病型ATL患者的循环ATL细胞上的那些。这表明，这些整合素的表达增加可能有助于淋巴瘤的形成。

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.