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Blood, 15 December 2003, Vol. 102, No. 13, pp. 4520-4526. Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2003-05-1455. This Article Full Text 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 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 Li, A. Articles by Gribben, J. G. Search for Related Content PubMed PubMed Citation Articles by Li, A. Articles by Gribben, J. G. Related Collections Immunobiology Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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 From the Division of Medical Oncology, Biostatistics, and Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA; the Department of Medicine, Brigham and Women's Hospital, Boston, MA; and the Division of Hematology/Oncology, Department of Medicine, The Children's Hospital, Harvard Medical School, Boston, MA, for the Dana-Farber ALL Consortium. 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, which has important implications for monitoring MRD, during the course of the disease. 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 8 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 retain the capacity to further differentiate into cells capable of altering the pattern of Ig and/or TCR rearrangements. (Blood. 2003;102:4520-4526) 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. Sensitive and Specific Measurement of Minimal Residual Disease in Acute Lymphoblastic Leukemia J. Mol. Diagn., May 1, 2009; 11(3): 201 - 210. [Abstract] [Full Text] [PDF] G. L. Chen and J. T. Prchal X-linked clonality testing: interpretation and limitations Blood, September 1, 2007; 110(5): 1411 - 1419. [Abstract] [Full Text] [PDF] J. Zhou, M. A Goldwasser, A. Li, S. E. Dahlberg, D. Neuberg, H. Wang, V. Dalton, K. D McBride, S. E. Sallan, L. B Silverman, et al. Quantitative analysis of minimal residual disease predicts relapse in children with B-lineage acute lymphoblastic leukemia in DFCI ALL Consortium Protocol 95-01 Blood, September 1, 2007; 110(5): 1607 - 1611. [Abstract] [Full Text] [PDF] S. Choi, M. J. Henderson, E. Kwan, A. H. Beesley, R. Sutton, A. Y. Bahar, J. Giles, N. C. Venn, L. D. Pozza, D. L. Baker, et al. Relapse in children with acute lymphoblastic leukemia involving selection of a preexisting drug-resistant subclone Blood, July 15, 2007; 110(2): 632 - 639. [Abstract] [Full Text] [PDF] A. Moghrabi, D. E. Levy, B. Asselin, R. Barr, L. Clavell, C. Hurwitz, Y. Samson, M. Schorin, V. K. Dalton, S. E. Lipshultz, et al. Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for children with acute lymphoblastic leukemia Blood, February 1, 2007; 109(3): 896 - 904. [Abstract] [Full Text] [PDF] E. R. Panzer-Grumayer, G. Cazzaniga, V. H.J. van der Velden, L. del Giudice, M. Peham, G. Mann, C. Eckert, A. Schrauder, G. Germano, J. Harbott, et al. Immunogenotype Changes Prevail in Relapses of Young Children with TEL-AML1-Positive Acute Lymphoblastic Leukemia and Derive Mainly from Clonal Selection Clin. Cancer Res., November 1, 2005; 11(21): 7720 - 7727. [Abstract] [Full Text] [PDF] T. Szczepanski, V. H. J. van der Velden, P. G. Hoogeveen, M. de Bie, D. C. H. Jacobs, E. R. van Wering, and J. J. M. van Dongen V{delta}2-J{alpha} rearrangements are frequent in precursor-B-acute lymphoblastic leukemia but rare in normal lymphoid cells Blood, May 15, 2004; 103(10): 3798 - 3804. [Abstract] [Full Text] [PDF]

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