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Blood, 15 July 2004, Vol. 104, No. 2, pp. 543-549. Prepublished online as a Blood First Edition Paper on March 25, 2004; DOI 10.1182/blood-2003-10-3545. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-10-3545v1 104/2/543    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 Guiter, C. Articles by Castellano, F. Search for Related Content PubMed PubMed Citation Articles by Guiter, C. Articles by Castellano, F. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Constitutive STAT6 activation in primary mediastinal large B-cell lymphoma Chrystelle Guiter, Isabelle Dusanter-Fourt, Christiane Copie-Bergman, Marie-Laure Boulland, Sabine le Gouvello, Philippe Gaulard, Karen Leroy, and Flavia Castellano From the U617, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris XII/Département de Pathologie, Créteil, France; U581, INSERM, Laboratoire d'Immunologie Biologique, Hôpital Henri Mondor, Créteil, France; and Unité INSERM 567/CNRS UMR 8104, Département d'Hématologie, Hôpital Cochin, Paris, France. Primary mediastinal large B-cell lymphoma (PMBL), currently recognized as a diffuse large B-cell lymphoma (DLBCL) subtype, shows increased expression of interleukin 4 (IL-4)/IL-13 signaling effectors and targets, suggesting constitutive activation of these pathways. We therefore investigated the functional state of the signal transducer and activator of transcription 6 (STAT6), mediating IL-4/IL-13 transcriptional effects. Constitutive STAT6 phosphorylation and DNA-binding activity were detected in PMBL cell lines but not DLBCL cell lines. Moreover, immunohistochemical analysis revealed nuclear phosphorylated STAT6 (P-STAT6) in 8 of 11 PMBL, compared with 1 of 10 DLBCL primary tumors (P = .01). IL-4 and IL-13 transcripts were absent in PMBL cell lines and expressed at low levels in tumors, indicating that, contrary to classical Hodgkin lymphoma (cHL), STAT6 activation is not due to an autocrine IL-4/IL-13 secretion. We demonstrated an amplification of the JAK2 gene in 2 of 6 PMBL cases, and showed higher JAK2 mRNA levels in PMBL compared with DLBCL (P = .005). The Janus kinase 2 (JAK2) was constitutively phosphorylated in the PMBL MedB1 cell line. MedB1 treatment with JAK2 inhibitor AG490 partially decreased STAT6 phosphorylation, suggesting that JAK2 is partially involved in STAT6 activation in these cells. Our findings highlight phosphorylated STAT6 as a characteristic distinguishing PMBL from DLBCL, but a common feature to PMBL and cHL, supporting the hypothesis of common pathogenic events in these 2 lymphomas. (Blood. 2004;104: 543-549) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. H. Cho, S. Goenka, T. Henttinen, P. Gudapati, A. Reinikainen, C. M. Eischen, R. Lahesmaa, and M. 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