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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 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 Citation Map 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 Hematopoiesis and Stem Cells Lymphoid Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Identification of cancer stem cells in a Tax-transgenic (Tax-Tg) mouse model of adult T-cell leukemia/lymphoma Jumpei Yamazaki1,2,*, Takuo Mizukami1,*, Kazuya Takizawa1, Madoka Kuramitsu1, Haruka Momose1, Atsuko Masumi1, Yasushi Ami3, Hideki Hasegawa4, William W. Hall5, Hajime Tsujimoto2, Isao Hamaguchi1, and Kazunari Yamaguchi1 1 Department of Safety Research on Blood and Biologics, National Institute of Infectious Diseases, Tokyo, Japan; 2 Veterinary Internal Medicine, University of Tokyo, Tokyo, Japan; Departments of 3 Animal Science and 4 Pathology, National Institute of Infectious Diseases, Tokyo, Japan; and 5 Centre for Research in Infectious Diseases, School of Medicine & Medical Science, University College Dublin, Dublin, Republic of Ireland 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 after transfer of Tax-Tg splenic lymphomatous cells (SLCs) to nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Using a limiting dilution transplantation, it was estimated that one CSC existed per 104 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 after transplantation of 102 SLCs, 102 CSCs could consistently regenerate the original lymphoma. In addition, lymphoma and CSCs could also be demonstrated in the bone marrow and CD117+ CSCs were observed in both osteoblastic and vascular niches. In the CSCs, Tax, Notch1, and Bmi1 expression was 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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