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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5101-5108. Prepublished online as a Blood First Edition Paper on March 7, 2008; DOI 10.1182/blood-2007-12-130229. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: blood-2007-12-130229v1 111/10/5101    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 CrossRef Google Scholar Articles by Ghia, E. M. Articles by Kipps, T. J. PubMed PubMed Citation Articles by Ghia, E. M. Articles by Kipps, T. J. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Use of IGHV3–21 in chronic lymphocytic leukemia is associated with high-risk disease and reflects antigen-driven, post–germinal center leukemogenic selection Emanuela M. Ghia1,2, Sonia Jain1,3, George F. Widhopf, II1,2, Laura Z. Rassenti1,2, Michael J. Keating1,4, William G. Wierda1,4, John G. Gribben1,5, Jennifer R. Brown1,6, Kanti R. Rai1,7, John C. Byrd1,8, Neil E. Kay1,9, Andrew W. Greaves1,2, and Thomas J. Kipps1,2 1 Chronic Lymphocytic Leukemia Research Consortium, La Jolla, CA; 2 Moores Cancer Center, Division of Hematology/Oncology and 3 Division of Biostatistics and Bioinformatics, University of California, San Diego, La Jolla; 4 Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston; 5 Barts and the London School of Medicine, London, United Kingdom; 6 Dana-Farber Cancer Institute, Boston, MA; 7 Long Island Jewish Medical Center, New Hyde Park, NY; 8 The Ohio State University, Columbus; and 9 Mayo Clinic, Rochester, MN We examined the chronic lymphocytic leukemia (CLL) cells of 2457 patients evaluated by the CLL Research Consortium (CRC) and found that 63 (2.6%) expressed immunoglobulin (Ig) encoded by the Ig heavy-chain-variable-region gene (IGHV), IGHV3-21. We identified the amino acid sequence DANGMDV (motif-1) or DPSFYSSSWTLFDY (motif-2) in the Ig heavy-chain (IgH) third complementarity-determining region (HCDR3) of IgH, respectively, used by 25 or 3 cases. The IgH with HCDR3 motif-1 or motif-2, respectively, was paired with Ig light chains (IgL) encoded by IGLV3-21 or IGKV3-20, suggesting that these Ig had been selected for binding to conventional antigen(s). Cases that had HCDR3 motif-1 had a median time from diagnosis to initial therapy comparable with that of cases without a defined HCDR3 motif, as did cases that used mutated IGHV3-21 (n = 27) versus unmutated IGHV3-21 (n = 30). Of 7 examined cases that used Ig encoded by IGHV3-21/IGLV3-21, we found that 5 had a functionally rearranged IGKV allele that apparently had incurred antigendriven somatic mutations and subsequent rearrangement with KDE. This study reveals that CLL cells expressing IGHV3-21/IGLV3-21 most likely were derived from B cells that had experienced somatic mutation and germinal-center maturation in an apparent antigen-driven immune response before undergoing Ig-receptor editing and after germinal-center leukemogenic selection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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