Adhesion-dependent growth of primary adult T cell leukemia cells with down-regulation of HTLV-I p40Tax protein: a novel in vitro model of the growth of acute ATL cells
Adhesion-dependent growth of primary adult T cell leukemia cells with down-regulation of HTLV-I p40Tax protein: a novel in vitro model of the growth of acute ATL cells
复制标题
HTLV-I p40Tax 蛋白下调的原代成体 T 细胞白血病细胞的粘附依赖性生长：急性 ATL 细胞生长的新型体外模型
DOI：
10.1007/s12185-008-0207-z
复制
发表时间：
2008
影响因子：
2.1
通讯作者：
M. Tomonaga
中科院分区：
文献类型：
--
作者：
K. Nagai;I. Jinnai;T. Hata;T. Usui;D. Sasaki;K. Tsukasaki;K. Sugahara;Y. Hishikawa;Yasuaki Yamada;Yuetsu Tanaka;T. Koji;H. Mano;S. Kamihira;M. Tomonaga
为了更好地了解成人T细胞白血病(ATL)的生物学特性，我们旨在建立一种新的方法，允许ATL细胞在与小鼠骨髓基质细胞MS-5共培养系统中进行原代培养。ATL细胞在与MS-5层紧密接触的情况下生长，并在没有IL-2的情况下形成所谓的“鹅卵石区”(CAS)。临床标本中，10例急性或淋巴瘤型ATL细胞中有8例(80.0%)形成CA。ATL细胞中CA形成率为0.03%~1.04%。形态、免疫表型和DNA分析表明，组成CA的细胞与ATL细胞相容，克隆上与原代CD4阳性ATL细胞相同。此外，在构成CA的ATL细胞中，p40Tax的表达在转录和翻译水平下调，而HTLV-I碱性亮氨酸拉链因子(HBZ)基因的表达水平与原代ATL细胞水平相当，与体内ATL细胞中前病毒基因的表达模式相似。通过基因芯片分析，与原代标本相比，在构成CA的ATL细胞中，有几个编码细胞间相互作用和细胞生存与增殖的编码产物的基因表达存在差异。总之，我们的共培养体系首次允许原代ATL细胞在体外生长，并可能作为一种体外实验用于生物学和临床研究，以开发针对ATL的分子靶向药物。
In order to better understand the biology of adult T cell leukemia (ATL), we aimed to establish a novel method, which allows the primary growth of ATL cells using a co-culture system with murine bone marrow-derived stromal cells, MS-5. ATL cells grew in close contact with MS-5 layers and formed so-called “cobblestone areas” (CAs) without the addition of IL-2. In clinical samples, eight of ten (80.0%) cases of acute or lymphoma type ATL cells formed CAs. The frequency of CA forming cells in ATL cells ranged from 0.03 to 1.04%. The morphology, immunophenotyping, and DNA analysis indicated that cells composing CA were compatible with ATL cells, and clonally identical to primary CD4-positive ATL cells. Furthermore, in ATL cells composing CA, the expression of p40Tax was down-regulated in transcriptional and translational level, while that of HTLV-I basic leucine zipper factor (HBZ) gene was comparable to the level of primary ATL cells, resembling expression pattern of proviral genes in in vivo ATL cells. By microarray analysis, several genes which coded products involved in cell–cell interaction, and cellular survival and proliferation, were differentially expressed in ATL cells composing CA compared with primary samples. In conclusion, our co-culture system allows for the first time the growth of primary ATL cells in vitro, and might be useful as an in vitro assay for biological and clinical studies to develop molecular targeting drugs against ATL.
影响因子：
32.4
作者：
Bajenoff, Marc;Egen, Jackson G.;Germain, Ronald N.
通讯作者：
Germain, Ronald N.