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Blood, 15 January 2007, Vol. 109, No. 2, pp. 674-682. Prepublished online as a Blood First Edition Paper on September 26, 2006; DOI 10.1182/blood-2006-06-030445. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: blood-2006-06-030445v1 109/2/674    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 Citing Articles via Google Scholar Google Scholar Articles by Cox, C. V. Articles by Blair, A. Search for Related Content PubMed PubMed Citation Articles by Cox, C. V. Articles by Blair, A. Related Collections Hematopoiesis and Stem Cells Neoplasia Free Research Articles Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Characterization of a progenitor cell population in childhood T-cell acute lymphoblastic leukemia Charlotte V. Cox1,2, Hannah M. Martin2, Pamela R. Kearns2, Paul Virgo3, Roger S. Evely4, and Allison Blair1,2, 1 Bristol Institute for Transfusion Sciences, University of Bristol, United Kingdom; 2 Department of Cellular and Molecular Medicine, University of Bristol, United Kingdom; 3 Department of Immunology, North Bristol National Health Service (NHS) Trust, United Kingdom; 4 Bristol Haematology and Oncology Centre, Bristol, United Kingdom A significant proportion of children with T-cell acute lymphoblastic leukemia (T-ALL) continue to fail therapy. Consequently, characterization of the cells that proliferate to maintain the disease should provide valuable information on the most relevant therapeutic targets. We have used in vitro suspension culture (SC) and nonobese diabetic–severe combined immune deficient (NOD/SCID) mouse assays to phenotypically characterize and purify T-ALL progenitor cells. Cells from 13 pediatric cases were maintained in vitro for at least 4 weeks and expanded in 8 cases. To characterize the progenitors, cells were sorted for expression of CD34 and CD4 or CD7 and the subfractions were evaluated in vitro and in vivo. The majority of cells capable of long-term proliferation in vitro were derived from the CD34+/CD4– and CD34+/CD7– subfractions. Moreover, the CD34+/CD4– or CD7– cells were the only subfractions capable of NOD/SCID engraftment. These T-ALL cells successfully repopulated secondary and tertiary recipients with equivalent levels of engraftment, demonstrating self-renewal ability. The immunophenotype and genotype of the original leukemia cells were preserved with serial passage in the NOD/SCID mice. These data demonstrate the long-term repopulating ability of the CD34+/CD4– and CD34+/CD7– subfractions in T-ALL and suggest that a cell with a more primitive phenotype was the target for leukemic transformation in these cases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Yamazaki, T. Mizukami, K. Takizawa, M. Kuramitsu, H. Momose, A. Masumi, Y. Ami, H. Hasegawa, W. W. Hall, H. Tsujimoto, et al. Identification of cancer stem cells in a Tax-transgenic (Tax-Tg) mouse model of adult T-cell leukemia/lymphoma Blood, September 24, 2009; 114(13): 2709 - 2720. [Abstract] [Full Text] [PDF] C. V. Cox, P. Diamanti, R. S. Evely, P. R. Kearns, and A. Blair Expression of CD133 on leukemia-initiating cells in childhood ALL Blood, April 2, 2009; 113(14): 3287 - 3296. [Abstract] [Full Text] [PDF] F. Armstrong, P. B. de la Grange, B. Gerby, M.-C. Rouyez, J. Calvo, M. Fontenay, N. Boissel, H. Dombret, A. Baruchel, J. Landman-Parker, et al. NOTCH is a key regulator of human T-cell acute leukemia initiating cell activity Blood, February 19, 2009; 113(8): 1730 - 1740. [Abstract] [Full Text] [PDF] G. J. L. Kaspers Win-WNT pathway in ALL Blood, April 15, 2007; 109(8): 3135 - 3136. [Full Text] [PDF]

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