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Blood, 1 January 2007, Vol. 109, No. 1, pp. 259-270. Prepublished online as a Blood First Edition Paper on September 19, 2006; DOI 10.1182/blood-2006-03-012948. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2006-03-012948v1 109/1/259    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 Stamatopoulos, K. Articles by Davi, F. Search for Related Content PubMed PubMed Citation Articles by Stamatopoulos, K. Articles by Davi, F. Related Collections Clinical Trials and Observations Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: pathogenetic implications and clinical correlations Kostas Stamatopoulos1, Chrysoula Belessi2, Carol Moreno3, Myriam Boudjograh4, Giuseppe Guida5, Tatjana Smilevska1, Lynda Belhoul4, Stefania Stella5, Niki Stavroyianni1, Marta Crespo3, Anastasia Hadzidimitriou2, Laurent Sutton6, Francesc Bosch3, Nikolaos Laoutaris2, Achilles Anagnostopoulos1, Emili Montserrat3, Athanasios Fassas1, Guillaume Dighiero7, Federico Caligaris-Cappio8, Hélène Merle-Béral4, Paolo Ghia8,, and Frédéric Davi4 1 Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece; 2 Hematology Department, Nikea General Hospital, Athens, Greece; 3 Institute of Hematology and Oncology and Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain; 4 Laboratory of Hematology and Université Pierre et Marie Curie, Hôpital Pitié-Salpètrière, Paris, France; 5 Institute for Cancer Research and Treatment, IRCC; Candiolo e Ospedale Mauriziano "Umberto I," Torino, Italy; 6 Department of Clinical Hematology, Hôpital Victor Dupouy, Argenteuil, France; 7 Unité d'Immuno-Hématologie et d'Hématopathologie, Institut Pasteur, Paris, France; and 8 Università Vita-Salute, San Raffaele and Istituto Scientifico San Raffaele, Milano, Italy The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is biased and characterized by the existence of subsets of cases with closely homologous ("stereotyped") complementarity-determining region 3 (CDR3) sequences. In the present series, 201 (21.9%) of 916 patients with CLL expressed IGHV genes that belonged to 1 of 48 different subsets of sequences with stereotyped heavy chain (H) CDR3. Twenty-six subsets comprised 3 or more sequences and were considered "confirmed." The remaining subsets comprised pairs of sequences and were considered "potential"; public database CLL sequences were found to be members of 9 of 22 "potential" subsets, thereby allowing us to consider them also "confirmed." The chance of belonging to a subset exceeded 35% for unmutated or selected IGHV genes (eg, IGHV1-69/3-21/4-39). Comparison to non-CLL public database sequences showed that HCDR3 restriction is "CLL-related." CLL cases with selected stereotyped immunoglobulins (IGs) were also found to share unique biologic and clinical features. In particular, cases expressing stereotyped IGHV4-39/IGKV1-39-1D-39 and IGHV4-34/IGKV2-30 were always IgG-switched. In addition, IGHV4-34/IGKV2-30 patients were younger and followed a strikingly indolent disease, contrasting other patients (eg, those expressing IGHV3-21/IGLV3-21) who experienced an aggressive disease, regardless of IGHV mutations. These findings suggest that a particular antigen-binding site can be critical in determining the clinical features and outcome for at least some CLL patients. 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] F. Forconi, E. Sozzi, D. Rossi, S. S. Sahota, T. Amato, D. Raspadori, L. Trentin, L. Leoncini, G. Gaidano, and F. Lauria Selective influences in the expressed immunoglobulin heavy and light chain gene repertoire in hairy cell leukemia Haematologica, May 1, 2008; 93(5): 697 - 705. [Abstract] [Full Text] [PDF] A. Lanemo Myhrinder, E. Hellqvist, E. Sidorova, A. Soderberg, H. Baxendale, C. Dahle, K. Willander, G. Tobin, E. Backman, O. Soderberg, et al. A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies Blood, April 1, 2008; 111(7): 3838 - 3848. [Abstract] [Full Text] [PDF] G. F. Widhopf II, C. J. Goldberg, T. L. Toy, L. Z. Rassenti, W. G. Wierda, J. C. Byrd, M. J. Keating, J. G. Gribben, K. R. Rai, and T. J. Kipps Nonstochastic pairing of immunoglobulin heavy and light chains expressed by chronic lymphocytic leukemia B cells is predicated on the heavy chain CDR3 Blood, March 15, 2008; 111(6): 3137 - 3144. [Abstract] [Full Text] [PDF] A. Athanasiadou, K. Stamatopoulos, M. Gaitatzi, N. Stavroyianni, A. Fassas, and A. Anagnostopoulos Recurrent cytogenetic findings in subsets of patients with chronic lymphocytic leukemia expressing IgG-switched stereotyped immunoglobulins Haematologica, March 1, 2008; 93(3): 473 - 474. [Abstract] [Full Text] [PDF] F. Murray, N. Darzentas, A. Hadzidimitriou, G. Tobin, M. Boudjogra, C. Scielzo, N. Laoutaris, K. Karlsson, F. Baran-Marzsak, A. Tsaftaris, et al. Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis Blood, February 1, 2008; 111(3): 1524 - 1533. [Abstract] [Full Text] [PDF] A. W. Hauswirth and U. Jager Impact of cytogenetic and molecular prognostic markers on the clinical management of chronic lymphocytic leukemia Haematologica, January 1, 2008; 93(1): 14 - 19. [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]

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