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Prepublished online as a Blood First Edition Paper on March 13, 2003; DOI 10.1182/blood-2002-11-3479. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-11-3479v1 101/10/4047    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 Walsh, S. H. Articles by Rosenquist, R. Search for Related Content PubMed PubMed Citation Articles by Walsh, S. H. Articles by Rosenquist, R. Related Collections Immunobiology Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2003, Vol. 101, No. 10, pp. 4047-4054 NEOPLASIA Mutated VH genes and preferential VH3-21 use define new subsets of mantle cell lymphoma Sarah H. Walsh, Mia Thorsélius, Anna Johnson, Ola Söderberg, Mats Jerkeman, Erik Björck, Inger Eriksson, Ulf Thunberg, Ola Landgren, Mats Ehinger, Eva Löfvenberg, Kristina Wallman, Gunilla Enblad, Birgitta Sander, Anna Porwit-MacDonald, Michael Dictor, Tor Olofsson, Christer Sundström, Göran Roos, and Richard Rosenquist From the Departments of Genetics and Pathology and of Oncology, Radiology and Clinical Immunology, Uppsala University; Departments of Oncology, Pathology, and Hematology, Lund University Hospital; Department of Medical Biosciences, Pathology, Umeå University; Departments of Medicine and of Microbiology, Pathology and Immunology, Division of Pathology, Karolinska Institutet at Huddinge University Hospital, Stockholm; Department of Medicine, Falun Hospital; and the Departments of Molecular Medicine, Hematology, and Pathology, Karolinska Hospital and Institutet, Stockholm, Sweden. Mantle cell lymphoma (MCL) is believed to originate from a naive B cell. However, we recently demonstrated that a subset of MCL displayed mutated VH genes. We also reported restricted use of certain VH genes. To assess the prognostic impact of these new findings, we performed VH gene analysis of 110 patients, revealing that 18 (16%) patients had mutated and 92 (84%) patients had unmutated VH genes. Because the mutation rate was low in the mutated group (2.2%-6.7%), further investigation of the germline VH gene in T cells from 5 patients with mutated VH genes was carried out; results showed that the unrearranged VH gene was identical to the published sequence. These data confirm that the base pair substitutions within the rearranged VH genes represent hypermutations, and indicate germinal center exposure. However, VH gene mutation status did not correlate with prognosis because there was no difference in clinical outcome between the unmutated and mutated groups. The most frequently used VH genes were VH3-21 (21 patients) and VH4-34 (19 patients). A novel finding was that VH3-21+ MCL almost exclusively expressed  light chains and displayed highly restricted use of the V3-19 gene. VH3-21+ patients had longer median survival than the remaining patients (53 vs 34 months; P = .03), but they tended to be younger at diagnosis. The combined use of VH3-21/V3-19 suggests a possible role for antigen(s) in the pathogenesis of these tumors and indicates that VH3-21+ patients constitute a new MCL entity. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Hadzidimitriou, N. Darzentas, F. Murray, T. Smilevska, E. Arvaniti, C. Tresoldi, A. Tsaftaris, N. Laoutaris, A. Anagnostopoulos, F. Davi, et al. Evidence for the significant role of immunoglobulin light chains in antigen recognition and selection in chronic lymphocytic leukemia Blood, January 8, 2009; 113(2): 403 - 411. [Abstract] [Full Text] [PDF] D. Kienle, T. Katzenberger, G. Ott, D. Saupe, A. Benner, H. Kohlhammer, T. F.E. Barth, S. Holler, J. Kalla, A. Rosenwald, et al. Quantitative Gene Expression Deregulation in Mantle-Cell Lymphoma: Correlation With Clinical and Biologic Factors J. Clin. Oncol., July 1, 2007; 25(19): 2770 - 2777. [Abstract] [Full Text] [PDF] M. Thorselius, A. Krober, F. Murray, U. Thunberg, G. Tobin, A. Buhler, D. Kienle, E. Albesiano, R. Maffei, L.-P. Dao-Ung, et al. Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status Blood, April 1, 2006; 107(7): 2889 - 2894. [Abstract] [Full Text] [PDF] R. J. Bende, W. M. Aarts, R. G. Riedl, D. de Jong, S. T. Pals, and C. J.M. van Noesel Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity J. Exp. Med., April 18, 2005; 201(8): 1229 - 1241. [Abstract] [Full Text] [PDF] A. Li, M. Rue, J. Zhou, H. Wang, M. A. Goldwasser, D. Neuberg, V. Dalton, D. Zuckerman, C. Lyons, L. B. Silverman, et al. 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 Blood, June 15, 2004; 103(12): 4602 - 4609. [Abstract] [Full Text] [PDF] D. Kienle, A. Krober, T. Katzenberger, G. Ott, E. Leupolt, T. F. E. Barth, P. Moller, A. Benner, A. Habermann, H. K. Muller-Hermelink, et al. VH mutation status and VDJ rearrangement structure in mantle cell lymphoma: correlation with genomic aberrations, clinical characteristics, and outcome Blood, October 15, 2003; 102(8): 3003 - 3009. [Abstract] [Full Text] [PDF]

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