Genes that influence the development of adult T-cell leukemia

点击翻译按钮获取中文摘要

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.