Abstract:
: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.
journal_name
Int J Hematoljournal_title
International journal of hematologyauthors
Nagai K,Jinnai I,Hata T,Usui T,Sasaki D,Tsukasaki K,Sugahara K,Hishikawa Y,Yamada Y,Tanaka Y,Koji T,Mano H,Kamihira S,Tomonaga Mdoi
10.1007/s12185-008-0207-zsubject
Has Abstractpub_date
2008-12-01 00:00:00pages
551-564issue
5eissn
0925-5710issn
1865-3774pii
10.1007/s12185-008-0207-zjournal_volume
88pub_type
杂志文章abstract::Ecotropic viral integration site-1 (EVI-1) has been recognized as one of the dominant oncogenes associated with murine and human myeloid leukemia. Recent clinical studies demonstrated that high EVI-1 expression was an independent negative prognostic indicator of survival in leukemia patients. In addition, gene-targeti...
journal_title:International journal of hematology
pub_type: 杂志文章,评审
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