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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1678-1685. Prepublished online as a Blood First Edition Paper on October 5, 2004; DOI 10.1182/blood-2004-07-2606. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-07-2606v1 105/4/1678    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 Ghia, P. Articles by Davi, F. Search for Related Content PubMed PubMed Citation Articles by Ghia, P. Articles by Davi, F. Related Collections Immunobiology Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Geographic patterns and pathogenetic implications of IGHV gene usage in chronic lymphocytic leukemia: the lesson of the IGHV3-21 gene Paolo Ghia, Kostas Stamatopoulos, Chrysoula Belessi, Carol Moreno, Stefania Stella, Giuseppe Guida, Ariane Michel, Marta Crespo, Nikolaos Laoutaris, Emili Montserrat, Achilles Anagnostopoulos, Guillaume Dighiero, Athanasios Fassas, Federico Caligaris-Cappio, and Frédéric Davi From the Department of Oncological Sciences, University of Torino and Institute for Cancer Research and Treatment, Torino, Italy; Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece; Hematology Department, Nikea General Hospital, Athens, Greece; Institute of Hematology and Oncology and Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Barcelona, Spain; Unité d'Immuno-Hématologie et d'Hématopathologie, Institut Pasteur, Paris, France; Department of Oncology, Università Vita Salute, San Raffaele, Milano, Italy; Laboratory of Hematology and University Paris 6, Hôpital Pitié-Salpètrière, Paris, France. We studied immunoglobulin variable heavy-chain (IGHV) repertoire and mutational status in 553 patients with chronic lymphocytic leukemia (CLL) from the Mediterranean area to gain insight into the potential pathogenetic role of antigenic stimulation. The most commonly represented IGHV genes mirrored the usage of normal B cells, with the exception of IGHV1-18, IGHV3-30.3, and IGHV4-59 that were underrepresented. The IGHV3-21 gene, frequently expressed in Northern European CLL, was present only in 16 cases (2.9%). Based on HCDR3 cluster analysis, cases using IGHV3-21 could be grouped in 2 subsets of similar frequency. The first one (7 of 16 cases) carried a similar HCDR3 amino acid sequence (common-HCDR3 subset), virtually identical to the Scandinavian IGHV3-21 CLL. These cases used the IGHJ6 gene; 4 of 7 were unmutated; 6 of 7 carried the V2-14 (IGLV3-21) light-chain gene with a similar LCDR3. All expressed CD38 and had a progressive disease. The second subset (9 of 16) was characterized by heterogeneous HCDR3 rearrangements (nonhomogeneous-HCDR3 subset), diverse IGHJ and IGV light-chain gene usage, variable IGHV mutational status (5 of 9 unmutated), variable CD38 expression, and variable clinical course (4 of 9 progressed). The first subset suggests a potential antigenic element rarely encountered in the Mediterranean area, possibly responsible for a negative outcome. The second subset may reflect the physiologic heterogeneity of expression of IGHV3-21 rearrangements in the normal repertoire and is characterized by a variable clinical outcome. (Blood. 2005;105:1678-1685) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L.-A. Sutton, E. Kostareli, A. Hadzidimitriou, N. Darzentas, A. Tsaftaris, A. Anagnostopoulos, R. Rosenquist, and K. Stamatopoulos Extensive intraclonal diversification in a subgroup of chronic lymphocytic leukemia patients with stereotyped IGHV4-34 receptors: implications for ongoing interactions with antigen Blood, November 12, 2009; 114(20): 4460 - 4468. [Abstract] [Full Text] [PDF] I. Del Giudice, S. Chiaretti, S. Tavolaro, M. S. De Propris, R. Maggio, F. Mancini, N. Peragine, S. Santangelo, M. Marinelli, F. R. Mauro, et al. 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