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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4602-4609. Prepublished online as a Blood First Edition Paper on March 9, 2004; DOI 10.1182/blood-2003-11-3857. This Article Full Text (PDF) All Versions of this Article: 2003-11-3857v1 103/12/4602    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?  Previous Article  |  Next Article  Submitted November 17, 2003 Accepted February 18, 2004 Utilization of Ig Heavy-Chain Variable, Diversity and Joining Gene Segments in Children with B-lineage Acute Lymphoblastic Leukemia: Implications for the Mechanisms of VDJ Recombination and for Pathogenesis Aihong Li, Montse Rue, Jianbiao Zhou, Hongjun Wang, Meredith A Goldwasser, Donna Neuberg, Virginia Dalton, David Zuckerman, Cheryl Lyons, Lewis B Silverman, Stephen E Sallan, and John G Gribben* Division of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Division of Biostatistical Science, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Department of Medicine, The Children's Hospital, Harvard Medical School, Boston, MA, USA Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA * Corresponding author; email: john_gribben{at}dfci.harvard.edu. Sequence analysis of the immunoglobulin heavy chain genes (IgH) has demonstrated preferential usage of specific variable (V), diversity (D) and joining (J) genes at different stages of B cell development and in B cell malignancies, and this has provided insight into B cell maturation and selection. Knowledge of the association between rearrangement patterns based on updated databases and clinical characteristics of pediatric acute lymphoblastic leukemia (ALL) is limited. We analyzed 381 IgH sequences identified at presentation in 317 children with B-lineage ALL and assessed the VHDHJH gene utilization profiles. The DHJH-proximal VH segments and the DH2 gene family were significantly over represented. Only 21% of VH-JH joinings were potentially productive, a finding associated with a trend towards an increased risk of relapse. These results suggest that physical location at the VH locus is involved in preferential usage of DHJH-proximal VH segments whereas DH and JH segments usage is governed by position-independent molecular mechanisms. Molecular pathophysiology appears relevant to clinical outcome in patients who have only productive rearrangements and specific rearrangement patterns are associated with differences in the tumor biology of childhood ALL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] K. M. Zirlik, D. Zahrieh, D. Neuberg, and J. G. Gribben Cytotoxic T cells generated against heteroclitic peptides kill primary tumor cells independent of the binding affinity of the native tumor antigen peptide Blood, December 1, 2006; 108(12): 3865 - 3870. [Abstract] [Full Text] [PDF]

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