权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Analysis of Expression of LAT1 in Childhood Leukemia and Effect of Inhibitors on Proliferation Inhibition

儿童白血病中LAT1的表达及抑制剂对增殖的抑制作用分析

基本信息

批准号：
13670836
负责人：
BESSHO Fumio
金额：
$ 1.92万
依托单位：
Kyorin University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2004
项目状态：
已结题

项目摘要

Expression of LAT1 was investigated for childhood leukemia cell lines and bone marrow cells from children with various kinds of leukemia at the diagnosis and during remission by Western blotting method, fluorescence-labeled antibody method and RT-PCR.Effect of BCH, one of inhibitors of LAT1, on cell liability was also investigated using MTT assay.Expression of LAT1 was found for all cell lines and bone marrow cells at diagnosis with all kinds of employed methods. Difference of expression of LAT1 was not observed among investigate leukemic cell lines with various biological natures and bone marrow leukemic cells with different prognoses and different cell types. Expression of LAT1 was also observed some of bone marrow cells during the remission phase.BCH could reduce liability of leukemic cell lines by dose-dependent manner. However, rate of reduction of liability decreased during increasing dose and LC_<50> could not be obtained by the BCH concentration of above 300 microM.Above result indicates necessity of stronger inhibitors to treat leukemia. Moreover, LAT1 was expressed on bone marrow cells during the remission. Since LAT1 is known to express on peripheral leukocytes and bone marrow, proliferation of normal bone marrow cells might be inhibited with LAT1 inhibitor. Other inhibitors with higher selectivity may be able to decrease liability more efficiently. Since currently available inhibitors with such characteristics are water insoluble, new inhibitors should be searched. Effects of inhibitors on hematopoietic stem cells are also needed to be tested in further studies.

采用免疫印迹法、荧光标记抗体法和RT-PCR法检测了儿童白血病细胞系及不同类型白血病患儿诊断期和缓解期骨髓细胞中LAT 1的表达，并观察了LAT 1抑制剂BCH对白血病细胞中LAT 1表达的影响。用MTT法检测细胞的敏感性，结果表明，在所有细胞系和骨髓细胞中，LAT 1均表达使用的方法。不同生物学特性的白血病细胞系及不同分化程度、不同细胞类型的骨髓白血病细胞中，LAT 1的表达无明显差异。结果表明，BCH能降低白血病细胞株的易感性，且呈剂量依赖性。但随着剂量的增加，白血病细胞的减毒率下降，<50>当BCH浓度超过300 μ M时，不能获得LC_2，提示需要更强的抑制剂治疗白血病。此外，在缓解期间，LAT 1在骨髓细胞上表达。由于已知LAT 1在外周血白细胞和骨髓上表达，因此LAT 1抑制剂可抑制正常骨髓细胞的增殖。具有更高选择性的其他抑制剂可能能够更有效地降低责任。由于目前可用的具有这些特性的抑制剂是水不溶性的，因此应寻找新的抑制剂。抑制剂对造血干细胞的影响也需要在进一步的研究中进行测试。