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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2002-01-0114. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-01-0114v1 100/3/948    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 Perfetti, V. Articles by Merlini, G. Search for Related Content PubMed PubMed Citation Articles by Perfetti, V. Articles by Merlini, G. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2002, Vol. 100, No. 3, pp. 948-953 IMMUNOBIOLOGY Analysis of V-J expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (III) as a new amyloid-associated germline gene segment Vittorio Perfetti, Simona Casarini, Giovanni Palladini, Maurizio Colli Vignarelli, Catherine Klersy, Marta Diegoli, Edoardo Ascari, and Giampaolo Merlini From Internal Medicine and Medical Oncology, Department of Internal Medicine, and Biometry and Clinical Epidemiology, Research Department, and Section of Human Pathology, Department of Human Pathology, and Biotechnology Research Laboratories, Department of Biochemistry, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy. Primary (AL) amyloidosis is a plasma cell dyscrasia characterized by extracellular deposition of monoclonal light-chain variable region (V) fragments in the form of amyloid fibrils. Light-chain amyloid is rare, and it is not fully understood why it occurs in only a fraction of patients with a circulating monoclonal component and why it typically associates with  isotype and VI family light-chain proteins. To provide insights into these issues, we obtained complete nucleotide sequences of monoclonal V regions from 55 consecutive unselected cases of primary amyloidosis and the results were compared with the light-chain expression profile of polyclonal marrow plasma cells from 3 healthy donors (a total of 264 sequences). We demonstrated that: (1) the III family is the most frequently used both in amyloidosis (47%) and in polyclonality (43%); (2) both conditions are characterized by gene restriction; (3) a very skewed repertoire is a feature of amyloidosis, because just 2 germline genes belonging to the III and VI families, namely 3r (22% of cases, III) and 6a (20%, VI), contributed equally to encode 42% of amyloid V regions; (4) these same 2 gene segments have a strong association with amyloidosis if their prevalences are compared with those in polyclonal conditions (3r, 8.3%, P = .024; 6a, 2.3%, P = .0008, 2 test); (5) the J2/3 segment, encoding the fourth framework region, appears to be slightly overrepresented in AL (83% versus 67%, P = .03), and this might be related to preferential J2/3 rearrangement in amyloid (11 of 12 cases) versus polyclonal 3r light chains (13 of 22 cases). These findings demonstrate that V-J expression is more restricted in plasma cells from amyloidosis than from polyclonal bone marrow and identify 3r as a new disease-associated gene segment. Overusage of just 2 gene segments, 3r and 6a, can thus account for the  light-chain overrepresentation typical of this disorder. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. L. Comenzo How I treat amyloidosis Blood, October 8, 2009; 114(15): 3147 - 3157. [Abstract] [Full Text] [PDF] B. K. Arendt, M. Ramirez-Alvarado, L. A. Sikkink, J. J. Keats, G. J. Ahmann, A. Dispenzieri, R. Fonseca, R. P. Ketterling, R. A. Knudson, E. M. Mulvihill, et al. Biologic and genetic characterization of the novel amyloidogenic lambda light chain-secreting human cell lines, ALMC-1 and ALMC-2 Blood, September 1, 2008; 112(5): 1931 - 1941. [Abstract] [Full Text] [PDF] E. M. Baden, B. A. 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	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020