SEARCH:   Advanced

Blood, 15 December 2008, Vol. 112, No. 13, pp. 5103-5110. Prepublished online as a Blood First Edition Paper on September 24, 2008; DOI 10.1182/blood-2008-04-150748. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-04-150748v1 112/13/5103    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 Citing Articles via Google Scholar Google Scholar Articles by Tjon, J. M. L. Articles by Koning, F. Search for Related Content PubMed PubMed Citation Articles by Tjon, J. M. L. Articles by Koning, F. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Defective synthesis or association of T-cell receptor chains underlies loss of surface T-cell receptor–CD3 expression in enteropathy-associated T-cell lymphoma Jennifer M. L. Tjon1, Wieke H. M. Verbeek2, Yvonne M. C. Kooy-Winkelaar1, Binh H. Nguyen1, Arno R. van der Slik1, Allan Thompson1, Mirjam H. M. Heemskerk3, Marco W. J. Schreurs4, Liesbeth H. A. Dekking1, Chris J. Mulder2, Jeroen van Bergen1, and Frits Koning1 1 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden; 2 Department of Gastroenterology, Free University Medical Center, Amsterdam; 3 Department of Hematology, Leiden University Medical Center, Leiden; and 4 Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands Enteropathy-associated T-cell lymphoma, an often fatal complication of celiac disease, can result from expansion of aberrant intraepithelial lymphocytes in refractory celiac disease type II (RCD II). Aberrant intraepithelial lymphocytes and lymphoma cells are intracellularly CD3+ but lack expression of the T-cell receptor (TCR)–CD3 complex on the cell surface. It is unknown what causes the loss of TCR-CD3 expression. We report the isolation of a cell line from an RCD II patient with the characteristic phenotype of enteropathy-associated T-cell lymphoma. We demonstrate that in this cell line the TCR- and -β chains as well as the CD3, CD3, CD3, and -chains are present intracellularly and that assembly of the CD3, CD3, and -dimers is normal. However, dimerization of the TCR chains and proper assembly of the TCR-CD3 complex are defective. On introduction of exogenous TCR-β chains, but not of TCR- chains, assembly and functional cell surface expression of the TCR-CD3 complex were restored. Defective synthesis of both TCR chains was found to underlie loss of TCR expression in similar cell lines isolated from 2 additional patients. (Pre)malignant transformation in RCD II thus correlates with defective synthesis or defective association of the TCR chains, resulting in loss of surface TCR-CD3 expression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020