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Blood, 24 September 2009, Vol. 114, No. 13, pp. 2709-2720. Prepublished online as a Blood First Edition Paper on July 7, 2009; DOI 10.1182/blood-2008-08-174425. This Article Full Text (PDF) All Versions of this Article: blood-2008-08-174425v1 114/13/2709    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Yamazaki, J. Articles by Yamaguchi, K. PubMed PubMed Citation Articles by Yamazaki, J. Articles by Yamaguchi, K. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 18, 2008 Accepted May 28, 2009 Identification of cancer stem cells in a Tax-transgenic (Tax-Tg) mouse model of adult T- cell leukemia / lymphoma (ATL) Jumpei Yamazaki, Takuo Mizukami, Kazuya Takizawa, Madoka Kuramitsu, Haruka Momose, Atsuko Masumi, Yasushi Ami, Hideki Hasegawa, William W. Hall, Hajime Tsujimoto, Isao Hamaguchi*, and Kazunari Yamaguchi Department of Safety Research on Blood and Biologics, National Institute of Infectious Diseases, Tokyo, Japan Department of Animal Science, National Institute of Infectious Diseases, Tokyo, Japan Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan Centre for Research in Infectious Diseases, School of Medicine & Medical Science, University College, Dublin, Belfield, Republic of Ireland Veterinary Internal Medicine, University of Tokyo, Tokyo, Japan * Corresponding author; email: 130hama{at}nih.go.jp. Adult T- Cell Leukemia / lymphoma (ATL) is a malignant lymphoproliferative disorder caused by HTLV-I infection. In ATL, chemotherapeutic responses are generally poor which has suggested the existence of chemotherapy-resistant cancer stem cells (CSCs). To identify CSC candidates in ATL, we have focused on a Tax transgenic mouse (Tax-Tg) model, which reproduces ATL-like disease both in Tax-Tg animals and also following transfer of Tax-Tg splenic lymphomatous cells (SLCs) to NOD/SCID mice. Using a limiting dilution transplantation, it was estimated that one CSC existed per 1x104 SLCs (0.01%). In agreement with this, we have successfully identified candidate CSCs in a side population (0.06%) which overlapped with a minor population of CD38-/CD71-/CD117+ cells (0.03%). Whereas lymphoma did not develop following transplantation of 1x102 SLCs, 1x102 CSCs could consistently regenerate the original lymphoma. In addition, lymphoma and CSCs could also be demonstrated in the bone marrow and CD117+ positive CSCs were observed in both osteoblastic and vascular niches. In the CSCs, Tax, Notch1 and Bmi-1 expression were down regulated, suggesting that the CSCs were derived from Pro-T cells or early hematopoietic progenitor cells. Taken together, our data demonstrate that CSCs certainly exist, and have the potential to regenerate lymphoma in our mouse model. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: "Tax-ing" the cancer stem cell Gerold Feuer Blood 2009 114: 2568-2569. [Full Text] [PDF] This article has been cited by other articles: G. Feuer "Tax-ing" the cancer stem cell Blood, September 24, 2009; 114(13): 2568 - 2569. [Full Text] [PDF]

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