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Blood, 12 November 2009, Vol. 114, No. 20, pp. 4460-4468. Prepublished online as a Blood First Edition Paper on August 27, 2009; DOI 10.1182/blood-2009-05-221309. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2009-05-221309v1 114/20/4460    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 Sutton, L.-A. Articles by Stamatopoulos, K. PubMed PubMed Citation Articles by Sutton, L.-A. Articles by Stamatopoulos, K. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Extensive intraclonal diversification in a subgroup of chronic lymphocytic leukemia patients with stereotyped IGHV4-34 receptors: implications for ongoing interactions with antigen Lesley-Ann Sutton1,*, Efterpi Kostareli2,3,*, Anastasia Hadzidimitriou4, Nikos Darzentas4, Athanasios Tsaftaris4, Achilles Anagnostopoulos3, Richard Rosenquist1, and Kostas Stamatopoulos3 1 Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; 2 Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3 Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece; and 4 Institute of Agrobiotechnology, Centre for Research and Technology, Thessaloniki, Greece Several studies indicate that the development of chronic lymphocytic leukemia (CLL) may be influenced by antigen recognition through the clonotypic B-cell receptors (BCRs). However, it is still unclear whether antigen involvement is restricted to the malignant transformation phase or whether the putative antigen(s) may continuously trigger the CLL clone and affect not only the progenitor cell but also the leukemic cells themselves. To address this issue, we conducted a large-scale subcloning study of rearranged immunoglobulin heavy variable (IGHV) genes of diverse mutational status from 71 CLL cases (total, 1496 subcloned sequences), belonging to both the common IgM/IgD variant and the rare IgG-positive variant. Although most cases showed no or low levels of intraclonal diversification (ID), we report intense ID in the IGHV genes of selected cases, especially a subgroup of 13 IgG-switched cases expressing stereotyped, mutated IGHV4-34 rearrangements (subset 4). We demonstrate that the ID evident in subset 4 cases cannot be attributed to IGHV4-34 usage, IGHV gene-mutated status, class-switch recombination, or BCR stereotypy in general; rather, it represents a unique phenomenon strongly correlated with the distinctive BCR of subset 4. In such cases, the observed ID patterns may imply a stereotyped response to an active, ongoing interaction with antigen(s). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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