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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-11-3485. This Article Full Text (PDF) All Versions of this Article: 2002-11-3485v1 101/12/4952    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 Tobin, G. Articles by Rosenquist, R. Search for Related Content PubMed PubMed Citation Articles by Tobin, G. Articles by Rosenquist, R. Social Bookmarking                   What's this? Submitted November 19, 2002 Accepted February 4, 2003 Chronic lymphocytic leukemias utilizing the VH3-21 gene display highly restricted V2-14 gene usage and homologous CDR3s: implicating recognition of a common antigen epitope Gerard Tobin, Ulf Thunberg, Anna Johnson, Inger Eriksson, Ola Soderberg, Karin Karlsson, Mats Merup, Gunnar Juliusson, Juhani Vilpo, Gunilla Enblad, Christer Sundstrom, Goran Roos, and Richard Rosenquist* Genetics and Pathology, Uppsala University, Uppsala, Sweden Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden Medical Biosciences, Patology, Umea University, Umea, Sweden Hematology, Linkoping University Hospital, Linkoping, Sweden Hematology, Huddinge University Hospital, Stockholm, Sweden Clinical Chemistry, Tampere University Hospital and Jorvi Hospital, Tammerfors, Finland * Corresponding author; email: richard.rosenquist{at}genpat.uu.se. The immunoglobulin variable heavy chain (IgVH) gene mutation status is an important prognostic factor in chronic lymphocytic leukemia (CLL), since cases with mutated VH genes show significantly longer survival than unmutated cases. Recently, we reported a preferential usage of the VH3-21 gene in mutated CLL and showed that mutated VH3-21 cases had an inferior overall survival compared to other mutated CLL. In order to further characterize this subset, we performed VH gene analysis in 265 CLL cases and identified 31 VH3-21 cases (11.7%); 21 cases had mutated and 10 cases unmutated VH genes. Regardless of the VH gene mutation status, a poor overall survival was found in the VH3-21 cases with a median survival of 83 months. This survival data confirms that VH3-21 cases do not fit into the general prognostic grouping of mutated and unmutated CLL. A large fraction of VH3-21 cases also demonstrated unique features with shorter lengths of the third complementarity region (CDR3) and CDR3s with highly homologous amino acid sequences. Furthermore, the VH3-21 cases showed a striking dominance of light chain expression and analysis of the Ig gene rearrangements revealed highly restricted usage of the V2-14/J3 genes in the majority of cases. Taken together, our new findings strengthen the suggestion that VH3-21 utilizing cases comprise a new CLL entity, irrespective of VH gene mutation status, and implicate that a common antigen epitope, perhaps of pathogenic significance, is recognized by the highly homologous VH3-21/V2-14 Ig molecules expressed in individual tumors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L.-A. Sutton, E. Kostareli, A. Hadzidimitriou, N. Darzentas, A. Tsaftaris, A. Anagnostopoulos, R. Rosenquist, and K. 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