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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3905-3914. Prepublished online as a Blood First Edition Paper on February 5, 2004; DOI 10.1182/blood-2003-08-2911. This Article Full Text (PDF) All Versions of this Article: 2003-08-2911v1 103/10/3905    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 Citing Articles via Google Scholar Google Scholar Articles by Liem, N. L Articles by Lock, R. B Search for Related Content PubMed PubMed Citation Articles by Liem, N. L Articles by Lock, R. B Social Bookmarking                   What's this? Submitted August 26, 2003 Accepted January 29, 2004 Characterization of childhood acute lymphoblastic leukemia xenograft models for the pre-clinical evaluation of new therapies Natalia L Liem, Rachael A Papa, Christopher G Milross, Michael A Schmid, Mayamin Tajbakhsh, Seoyeon Choi, Carole D Ramirez, Alison M Rice, Michelle Haber, Murray D Norris, Karen L MacKenzie, and Richard B Lock* Children's Cancer Institute Australia for Medical Research, Sydney, NSW, Australia; School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia Children's Cancer Institute Australia for Medical Research, Sydney, NSW, Australia Department of Radiation Oncology, Prince of Wales Hospital, Sydney, NSW, Australia Mater Medical Research Institute, Brisbane, QLD, Australia * Corresponding author; email: richard.lock{at}unsw.edu.au. Continuous xenografts from 10 children with acute lymphoblastic leukemia (ALL) were established in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Relative to primary engrafted cells, negligible changes in growth rates and immunophenotype were observed at second and third passage. Analysis of clonal antigen receptor gene rearrangements in 2 xenografts from patients at diagnosis showed that the pattern of clonal variation observed following tertiary transplantation in mice exactly reflected that in bone marrow samples at the time of clinical relapse. Patients experienced diverse treatment outcomes, including 5 who died of disease (median 13 months, range 11-76, from date of diagnosis), and 5 who remain alive (median 103 months, range 56-131, following diagnosis). When stratified according to patient outcome the in vivo sensitivity of xenografts to vincristine and dexamethasone, but not methotrexate, differed significantly (P = 0.028, 0.029 and 0.56, respectively). The in vitro sensitivity of xenografts to dexamethasone, but not vincristine, correlated significantly with in vivo responses and patient outcome. This study shows, for the first time, that the biological and genetic characteristics, and patterns of chemosensitivity, of childhood ALL xenografts accurately reflect the clinical disease. As such, they provide powerful experimental models to prioritize new therapeutic strategies for future clinical trials. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. W. Behan, J. P. Yun, M. P. Proektor, E. A. Ehsanipour, A. Arutyunyan, A. S. Moses, V. I. Avramis, S. G. Louie, A. Butturini, N. Heisterkamp, et al. Adipocytes Impair Leukemia Treatment in Mice Cancer Res., October 1, 2009; 69(19): 7867 - 7874. [Abstract] [Full Text] [PDF] C. V. Cox, P. Diamanti, R. S. Evely, P. R. Kearns, and A. 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