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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2499-2504. Prepublished online as a Blood First Edition Paper on June 24, 2004; DOI 10.1182/blood-2004-03-0818. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-0818v1 104/8/2499    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 Widhopf, G. F. Articles by Kipps, T. J. Search for Related Content PubMed PubMed Citation Articles by Widhopf, G. F., II Articles by Kipps, T. J. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins George F. Widhopf, II, Laura Z. Rassenti, Traci L. Toy, John G. Gribben, William G. Wierda, and Thomas J. Kipps From the Division of Hematology/Oncology, Department of Medicine, University of California, San Diego, La Jolla, CA; the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; the Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX; and the CLL Research Consortium, University of California, San Diego. We examined the immunoglobulin (Ig) heavy chain variable region genes (VH genes) used by leukemia cells of 1220 unrelated patients with chronic lymphocytic leukemia (CLL). We found 1188 (97%) expressed Ig encoded by a single Ig VH subgroup, the most common of which was VH3 (571 or 48.1%), followed by VH1 (319 or 26.8%) and VH4 (241 or 20.2%). Using allele-specific primers, we found 13.8% of all samples (n = 164) used one major VH1-69 allele, designated 51p1, 163 of which were not somatically mutated. For these cases, there was marked restriction in the structure of the Ig third complementarity determining regions (CDR3s), which were encoded by a small number of unmutated D and JH gene segments. Strikingly, 15 of the 163 cases had virtually identical CDR3s encoded by the second reading frame of D3-16 and JH3. Further analysis revealed that each of these 15 samples used the same unmutated Ig kappa light-chain gene, namely A27. These data reveal that approximately 1.3% (15/1220) of all patients had leukemia cells that expressed virtually identical Ig. This finding provides compelling evidence that the Ig expressed by CLL B cells are highly selected and not representative of the Ig expressed by naive B cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Muzio, B. Apollonio, C. Scielzo, M. Frenquelli, I. Vandoni, V. Boussiotis, F. Caligaris-Cappio, and P. Ghia Constitutive activation of distinct BCR-signaling pathways in a subset of CLL patients: a molecular signature of anergy Blood, July 1, 2008; 112(1): 188 - 195. [Abstract] [Full Text] [PDF] 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] G. F. Widhopf II, C. J. 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