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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2889-2894. Prepublished online as a Blood First Edition Paper on November 29, 2005; DOI 10.1182/blood-2005-06-2227. This Article Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: 2005-06-2227v1 107/7/2889    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 Thorselius, M. Articles by Rosenquist, R. Search for Related Content PubMed PubMed Citation Articles by Thorselius, M. Articles by Rosenquist, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 3, 2005 Accepted November 14, 2005 Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-utilizing chronic lymphocytic leukemia independent of geographical origin and mutational status Mia Thorselius, Alexander Krober, Fiona Murray, Ulf Thunberg, Gerard Tobin, Andreas Buhler, Dirk Kienle, Emilia Albesiano, Rossana Maffei, Lan-Phuong Dao-Ung, James Wiley, Juhani Vilpo, Anna Laurell, Mats Merup, Goran Roos, Karin Karlsson, Nicholas Chiorazzi, Roberto Marasca, Hartmut Dohner, Stephan Stilgenbauer, and Richard Rosenquist* Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden Department of Internal Medicine III, University of Ulm, Ulm, Germany Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden Institute for Medical Research, North Shore - LIJ Health System and Departments of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, USA Department of Oncology and Hematology, University of Modena and Reggio E, Modena, Italy Department of Medicine, University of Sydney, Nepean Hospital, Penrith, Australia Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland Department of Medicine, Karolinska University Hospital, Huddinge, Sweden Department of Medical Biosciences, Pathology, Umea University, Umea, Sweden Department of Hematology, Linkoping University Hospital, Linkoping, Sweden * Corresponding author; email: richard.rosenquist{at}genpat.uu.se. We recently reported that Swedish VH3-21-utilizing chronic lymphocytic leukemia (CLL) patients showed restricted immunoglobulin gene features and poor prognosis despite VH mutation status. To investigate this further, we analyzed the VH and VL gene rearrangements in 90 VH3-21+ patients from Sweden, Germany, Italy, USA, Finland and Australia and correlated these data with survival and other prognostic markers. Sixty-three percent exhibited mutated VH genes and 37% unmutated VH genes. Fifty patients (56%) displayed a short and homologous heavy-chain CDR3, many of these with the amino acid motif, DANGMDV. Also, a highly biased V2-14 usage was evident in 72% of patients with a restricted light-chain CDR3, QVWDS(S/G)SDHPWV. Combined restricted heavy- and light-chain CDR3s were found in patients from all included countries. Although VH3-21+ CLLs have a remarkably predominant -expression, analyses of kappa deleting element indicated a conserved light-chain rearrangement order. The overall survival was poor in the VH3-21+ cohort (median survival 88 months) with no significant difference in relation to mutation status or CDR3 homology. High ZAP-70 and CD38 expression was found in both mutated and unmutated VH3-21+ cases as well as a slight increase of 11q- aberrations. In summary, highly restricted B-cell receptors and worse outcome characterize VH3-21+ CLLs independent of geographical origin and mutation status. 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. Stamatopoulos Extensive intraclonal diversification in a subgroup of chronic lymphocytic leukemia patients with stereotyped IGHV4-34 receptors: implications for ongoing interactions with antigen Blood, November 12, 2009; 114(20): 4460 - 4468. [Abstract] [Full Text] [PDF] O. Landgren, M. Albitar, W. Ma, F. 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