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Blood, 15 July 2007, Vol. 110, No. 2, pp. 632-639. Prepublished online as a Blood First Edition Paper on March 19, 2007; DOI 10.1182/blood-2007-01-067785. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-01-067785v1 110/2/632    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Choi, S. Articles by Norris, M. D. Search for Related Content PubMed PubMed Citation Articles by Choi, S. Articles by Norris, M. D. Related Collections Clinical Trials and Observations Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Relapse in children with acute lymphoblastic leukemia involving selection of a preexisting drug-resistant subclone Seoyeon Choi1, Michelle J. Henderson1, Edward Kwan1, Alex H. Beesley2, Rosemary Sutton1, Anita Y. Bahar1, Jodie Giles1, Nicola C. Venn1, Luciano Dalla Pozza3, David L. Baker4, Glenn M. Marshall1,5, Ursula R. Kees2, Michelle Haber1, and Murray D. Norris1 1 Children's Cancer Institute Australia for Medical Research, Sydney; 2 Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth; 3 Oncology Unit, The Children's Hospital, Westmead, Sydney; 4 Department of Haematology–Oncology, Princess Margaret Hospital, Perth; and 5 Centre for Children's Cancer and Blood Disorders, Sydney Children's Hospital, Randwick, Sydney, Australia Relapse following remission induction chemotherapy remains a barrier to survival in approximately 20% of children suffering from acute lymphoblastic leukemia (ALL). To investigate the mechanism of relapse, 27 matched diagnosis and relapse ALL samples were analyzed for clonal populations using polymerase chain reaction (PCR)–based detection of multiple antigen receptor gene rearrangements. These clonal markers revealed the emergence of apparently new populations at relapse in 13 patients. More sensitive clone-specific PCR revealed that, in 8 cases, these "relapse clones" were present at diagnosis and a significant relationship existed between presence of the relapse clone at diagnosis and time to first relapse (P < .007). Furthermore, in cases where the relapse clone could be quantified, time to first relapse was dependent on the amount of the relapse clone at diagnosis (r = –0.84; P = .018). This observation, together with demonstrated differential chemosensitivity between subclones at diagnosis, argues against therapy-induced acquired resistance as the mechanism of relapse in the informative patients. Instead these data indicate that relapse in ALL patients may commonly involve selection of a minor intrinsically resistant subclone that is undetectable by routine PCR-based methods. Relapse prediction may be improved with strategies to detect minor potentially resistant subclones early during treatment, hence allowing intensification of therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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