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Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2003-05-1455. This Article Full Text (PDF) All Versions of this Article: 2003-05-1455v1 102/13/4520    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 Li, A. Articles by Gribben, J. G Search for Related Content PubMed PubMed Citation Articles by Li, A. Articles by Gribben, J. G Social Bookmarking                   What's this? Submitted May 8, 2003 Accepted August 4, 2003 Sequence analysis of clonal immunoglobulin and T-cell receptor gene rearrangements in children with acute lymphoblastic leukemia at diagnosis and at relapse: implications for pathogenesis and for the clinical utility of PCR-based methods of minimal residual disease detection Aihong Li, Jianbiao Zhou, David Zuckerman, Montse Rue, Virginia Dalton, Cheryl Lyons, Lewis B Silverman, Stephen E Sallan, and John G Gribben* Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Division of Biostatistics, Dana-Farber Cancer Institute, Boston, MA, USA Division of Hematology/Oncology, Department of Medicine, The Children's Hospital, Boston, MA, USA * Corresponding author; email: john_gribben{at}dfci.harvard.edu. Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements provide clonal markers useful for diagnosis and measurement of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). We analyzed the sequences of Ig and TCR gene rearrangements obtained at presentation and relapse in 41 children with ALL to study clonal stability during the course of the disease, which has important implications for monitoring MRD. In 42%, all original Ig and/or TCR sequences were conserved. In 24%, one original sequence was preserved but the other lost, and in 14% the original sequences were conserved with new sequences identified at relapse. In 20% only new sequences were found at relapse. Using primers designed from the novel relapse sequences, the relapse clone could be identified as subdominant clones in the diagnostic sample in eight of 14 patients. Alteration of these clonal gene rearrangements is a common feature in childhood ALL. MRD detection should include multiple gene targets to minimize false negative samples or include also multicolor flow cytometry. In some cases the leukemic progenitor cell might arise earlier in lineage before DHJH recombination but retaining the capacity to further differentiate into cells capable of altering the pattern of Ig and/or TCR rearrangements. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. J. Brisco, S. Latham, R. Sutton, E. Hughes, V. Wilczek, K. van Zanten, B. Budgen, A. Y. Bahar, M. Malec, P. J. Sykes, et al. Determining the Repertoire of IGH Gene Rearrangements to Develop Molecular Markers for Minimal Residual Disease in B-Lineage Acute Lymphoblastic Leukemia J. Mol. Diagn., May 1, 2009; 11(3): 194 - 200. [Abstract] [Full Text] [PDF] A. A. Morley, S. Latham, M. J. Brisco, P. J. Sykes, R. Sutton, E. Hughes, V. Wilczek, B. Budgen, K. van Zanten, B. J. Kuss, et al. 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