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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3312-3317. Prepublished online as a Blood First Edition Paper on July 29, 2004; DOI 10.1182/blood-2004-03-0950. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-0950v1 104/10/3312    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 Forconi, F. Articles by Stevenson, F. K. Search for Related Content PubMed PubMed Citation Articles by Forconi, F. Articles by Stevenson, F. K. Related Collections Immunobiology Neoplasia Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Hairy cell leukemia: at the crossroad of somatic mutation and isotype switch Francesco Forconi, Surinder S. Sahota, Donatella Raspadori, Micaela Ippoliti, Gavin Babbage, Francesco Lauria, and Freda K. Stevenson From the Unità Operativa Complessa (UOC) Ematologia e Trapianti, Dipartimento di Medicina Clinica e Scienze Immunologiche, Università di Siena, Siena, Italy; and the Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals, Southampton, United Kingdom. Hairy cell leukemia (HCL) commonly expresses multiple immunoglobulin isotypes, a feature rare in other B-cell malignancies or in normal B cells. In HCL, there is no phenotypic evidence for subpopulations, and single cells from one previous case contained transcripts for several isotypes. This raises the questions of the differentiation status of the cell of origin and of posttransformation events. We have investigated 9 cases, all expressing multiple immunoglobulin isotypes. Multiple tumor-derived variable-(diversity)-joining-constant µ , , (V(D)J-Cµ, , , ) transcripts were confirmed in single cells of a further case. All cases were negative for germinal center (GC)-associated markers CD27 and CD38. Seven of 9 cases had mutated VH genes, with low levels of intraclonal heterogeneity, but 2 of 9 were unmutated, indicative of pre-GC origin. Eight of 9 cases expressed activation-induced cytidine deaminase (AID), a molecule essential for somatic mutation and isotype switch. All cases expressed germ line heavy-chain I exon (IH)-CH transcripts which paralleled surface immunoglobulin (sIg) isotype. Significantly, no circle transcripts indicative of deletional recombination of switched isotypes were detectable in 9 of 9 cases. These data indicate heterogeneity in the cell of origin in terms of mutational status, but reveal common features of AID expression and isotype-switching events occurring prior to deletional recombination. Both mutational and switching events may be influenced by environmental factors at extrafollicular sites. (Blood. 2004;104:3312-3317) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Dissociation of AID expression and activity Ralf Küppers Blood 2004 104: 3001-3002. [Full Text] [PDF] This article has been cited by other articles: X. Wu, J. R. Darce, S. K. Chang, G. S. Nowakowski, and D. F. Jelinek Alternative splicing regulates activation-induced cytidine deaminase (AID): implications for suppression of AID mutagenic activity in normal and malignant B cells Blood, December 1, 2008; 112(12): 4675 - 4682. [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. Traverse-Glehen, L. Baseggio, E. C. Bauchu, D. Morel, S. Gazzo, M. Ffrench, A. Verney, D. Rolland, C. Thieblemont, J.-P. Magaud, et al. Splenic red pulp lymphoma with numerous basophilic villous lymphocytes: a distinct clinicopathologic and molecular entity? Blood, February 15, 2008; 111(4): 2253 - 2260. [Abstract] [Full Text] [PDF] S. W. Popov, G. Moldenhauer, B. Wotschke, S. Bruderlein, T. F. Barth, K. Dorsch, O. Ritz, P. Moller, and F. Leithauser Target Sequence Accessibility Limits Activation-Induced Cytidine Deaminase Activity in Primary Mediastinal B-Cell Lymphoma Cancer Res., July 15, 2007; 67(14): 6555 - 6564. [Abstract] [Full Text] [PDF] C. Wei, J. Anolik, A. Cappione, B. Zheng, A. Pugh-Bernard, J. Brooks, E.-H. Lee, E. C. B. Milner, and I. Sanz A New Population of Cells Lacking Expression of CD27 Represents a Notable Component of the B Cell Memory Compartment in Systemic Lupus Erythematosus J. Immunol., May 15, 2007; 178(10): 6624 - 6633. [Abstract] [Full Text] [PDF] A. Kotani, N. Kakazu, T. Tsuruyama, I.-m. Okazaki, M. Muramatsu, K. Kinoshita, H. Nagaoka, D. Yabe, and T. Honjo Activation-induced cytidine deaminase (AID) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice PNAS, January 30, 2007; 104(5): 1616 - 1620. [Abstract] [Full Text] [PDF] P. Bergqvist, E. Gardby, A. Stensson, M. Bemark, and N. Y. Lycke Gut IgA Class Switch Recombination in the Absence of CD40 Does Not Occur in the Lamina Propria and Is Independent of Germinal Centers J. Immunol., December 1, 2006; 177(11): 7772 - 7783. [Abstract] [Full Text] [PDF] J. F. Fecteau, G. Cote, and S. Neron A New Memory CD27-IgG+ B Cell Population in Peripheral Blood Expressing VH Genes with Low Frequency of Somatic Mutation J. Immunol., September 15, 2006; 177(6): 3728 - 3736. [Abstract] [Full Text] [PDF] S. O. Wanko and C. de Castro Hairy Cell Leukemia: An Elusive but Treatable Disease Oncologist, July 1, 2006; 11(7): 780 - 789. [Abstract] [Full Text] [PDF] F. Ravandi, J. L. Jorgensen, S. M. O'Brien, S. Verstovsek, C. A. Koller, S. Faderl, F. J. Giles, A. Ferrajoli, W. G. Wierda, S. Odinga, et al. Eradication of minimal residual disease in hairy cell leukemia Blood, June 15, 2006; 107(12): 4658 - 4662. [Abstract] [Full Text] [PDF] G. Babbage, C. H. Ottensmeier, J. Blaydes, F. K. Stevenson, and S. S. Sahota Immunoglobulin heavy chain locus events and expression of activation-induced cytidine deaminase in epithelial breast cancer cell lines. Cancer Res., April 15, 2006; 66(8): 3996 - 4000. [Abstract] [Full Text] [PDF] F. Ravandi and S. O'Brien Chronic Lymphoid Leukemias Other Than Chronic Lymphocytic Leukemia: Diagnosis and Treatment Mayo Clin. Proc., December 1, 2005; 80(12): 1660 - 1674. 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