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Blood, 15 July 2005, Vol. 106, No. 2, pp. 681-689. Prepublished online as a Blood First Edition Paper on April 7, 2005; DOI 10.1182/blood-2004-10-4073. This Article Full Text (PDF) Supplemental Figures and Tables All Versions of this Article: 2004-10-4073v1 106/2/681    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 Falt, S. Articles by Wennborg, A. Search for Related Content PubMed PubMed Citation Articles by Falt, S. Articles by Wennborg, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 22, 2004 Accepted March 18, 2005 Distinctive gene expression pattern in VH3-21 utilizing B-cell chronic lymphocytic leukemia Susann Falt*, Mats Merup, Gerard Tobin, Ulf Thunberg, Gosta Gahrton, Richard Rosenquist, and Anders Wennborg Unit of Environmental Medicine, Center for Nutrition and Toxicology, Department of Biosciences at Novum, Karolinska Institutet, Huddinge, Stockholm, Sweden Department of Hematology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden * Corresponding author; email: susann.falt{at}biosci.ki.se. The usage of the immunoglobulin (Ig) VH3-21 gene is associated with poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) despite VH gene mutation status. Many VH3-21+ patients also display restricted heavy and light chain Ig gene rearrangements, implying a role of antigen selection in disease development. To explore the specific phenotypic/genotypic features among VH3-21+ B-CLLs, we compared gene expression patterns in 15 VH3-21+ and 24 non-VH3-21 patients (11 with unmutated and 13 with mutated VH genes) using Affymetrix microarray analysis (~12.500 genes). A distinct expression profile was identified for VH3-21+ patients in contrast to the Ig-unmutated and mutated groups. By applying different algorithms, the data enabled an efficient class discrimination of the VH3-21+ subset based on 27 or 57 genes. A set of genes was sorted out which, using different analytical methods, consistently gave a distinction between VH3-21+ and non-VH3-21 samples. Several of these genes are involved in regulation of DNA replication/cell cycle control, transcription and protein kinase activity, which may render the VH3-21+ cells with a higher proliferative drive. However, no clear evidence of increased B-cell receptor signaling was found in the VH3-21+ group. Altogether, our identification of a specific "VH3-21 profile" may provide insights into the pathogenesis of the VH3-21+ subgroup. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. M. Ghia, S. Jain, G. F. Widhopf II, L. Z. Rassenti, M. J. Keating, W. G. Wierda, J. G. Gribben, J. R. Brown, K. R. Rai, J. C. Byrd, et al. Use of IGHV3-21 in chronic lymphocytic leukemia is associated with high-risk disease and reflects antigen-driven, post-germinal center leukemogenic selection Blood, May 15, 2008; 111(10): 5101 - 5108. [Abstract] [Full Text] [PDF] R. Bomben, M. Dal Bo, D. Capello, D. Benedetti, D. Marconi, A. Zucchetto, F. Forconi, R. Maffei, E. M. Ghia, L. Laurenti, et al. Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study Blood, April 1, 2007; 109(7): 2989 - 2998. [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] D. Kienle, A. Benner, A. Krober, D. Winkler, D. Mertens, A. Buhler, T. Seiler, U. Jager, P. Lichter, H. Dohner, et al. Distinct gene expression patterns in chronic lymphocytic leukemia defined by usage of specific VH genes Blood, March 1, 2006; 107(5): 2090 - 2093. [Abstract] [Full Text] [PDF]

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