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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3490-3495. Prepublished online as a Blood First Edition Paper on December 24, 2003; DOI 10.1182/blood-2003-10-3407. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-10-3407v1 103/9/3490    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 Messmer, B. T. Articles by Chiorazzi, N. Search for Related Content PubMed PubMed Citation Articles by Messmer, B. T. Articles by Chiorazzi, N. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA The pattern and distribution of immunoglobulin VH gene mutations in chronic lymphocytic leukemia B cells are consistent with the canonical somatic hypermutation process Bradley T. Messmer, Emilia Albesiano, Davorka Messmer, and Nicholas Chiorazzi From the North Shore-Long Island Jewish (LIJ) Research Institute, Manhasset, NY; and Departments of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, NY. The overexpanded clone in most B-cell-type chronic lymphocytic leukemia (BCLL) patients expresses an immunoglobulin (Ig) heavy chain variable (VH) region gene with some level of mutation. While it is presumed that these mutations were introduced in the progenitor cell of the leukemic clone by the canonical somatic hypermutation (SHM) process, direct evidence of such is lacking. Nucleotide sequences of the Ig VH genes from 172 B-CLL patients were analyzed. Previously described VH gene usage biases were noted. As with canonical SHM, mutations found in B-CLL were more frequent in RGYW hot spots (mutations in an RGYW motif = 44.1%; germ line frequency of RGYW motifs = 25.6%) and favored transitions over transversions (transition-transversion ratio = 1.29). Significantly, transition preference was also noted when only mutations in the wobble position of degenerate codons were considered. Wobble positions are inherently unselected since regardless of change an identical amino acid is encoded; therefore, they represent a window into the nucleotide bias of the mutational mechanism. B-CLL VH mutations concentrated in complementarity-determining region 1 (CDR1) and CDR2, which exhibited higher replacement-to-silent ratios (CDR R/S, 4.60; framework region [FR] R/S, 1.72). These results are consistent with the notion that VH mutations in B-CLL cells result from canonical SHM and select for altered, structurally sound antigen receptors. (Blood. 2004;103:3490-3495) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] O. Landgren, J. S. Rapkin, N. E. Caporaso, L. Mellemkjaer, G. Gridley, L. R. Goldin, and E. A. Engels Respiratory tract infections and subsequent risk of chronic lymphocytic leukemia Blood, March 1, 2007; 109(5): 2198 - 2201. [Abstract] [Full Text] [PDF] J. F. Fecteau, G. Cote, and S. 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Gandini, P. D. Sherrington, A. Mehta, A. V. Hoffbrand, and L. Foroni Conserved Amino Acid Sequences Occur in a Limited Group of CLL Patients with Predominantly Mutated IGH Rearrangements. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 2000 - 2000. [Abstract] G. Tobin, U. Thunberg, K. Karlsson, F. Murray, A. Laurell, K. Willander, G. Enblad, M. Merup, J. Vilpo, G. Juliusson, et al. Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia Blood, November 1, 2004; 104(9): 2879 - 2885. [Abstract] [Full Text] [PDF]

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