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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 16, 2003 Accepted March 13, 2004 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* Pathologie, U617, INSERM, Universite Paris XII, Hopital Henri Mondor, Creteil, France Hematologie, U567 INSERM/CNRS UMR 8104, Hopital Cochin, Paris, France Immunologie Biologique, U581, INSERM, Hopital Henri Mondor, Creteil, France * Corresponding author; email: Flavia.Castellano{at}im3.inserm.fr. 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)/13 (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, but not DLBCL cell lines. Moreover, immunohistochemical analysis revealed nuclear P-STAT6 in 8/11 PMBL, compared to 1/10 DLBCL primary tumors (p= 0.01). 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 2/6 PMBL cases, and showed higher JAK2 mRNA levels in PMBL compared to DLBCL (p= 0.005). The JAK2 kinase 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 phoshorylated 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 two lymphomas. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. A. Frank STAT6 in PMBL: pathogenic or passenger? Blood, August 6, 2009; 114(6): 1133 - 1134. [Full Text] [PDF] O. Ritz, C. Guiter, F. Castellano, K. Dorsch, J. Melzner, J.-P. Jais, G. Dubois, P. Gaulard, P. Moller, and K. Leroy Recurrent mutations of the STAT6 DNA binding domain in primary mediastinal B-cell lymphoma Blood, August 6, 2009; 114(6): 1236 - 1242. [Abstract] [Full Text] [PDF] S. H. Cho, S. Goenka, T. Henttinen, P. Gudapati, A. Reinikainen, C. M. Eischen, R. 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