SEARCH:   Advanced

This Article Full Text Full Text (PDF) 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 Skinnider, B. F. Articles by Mak, T. W. Search for Related Content PubMed PubMed Citation Articles by Skinnider, B. F. Articles by Mak, T. W. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 January 2002, Vol. 99, No. 2, pp. 618-626 NEOPLASIA Signal transducer and activator of transcription 6 is frequently activated in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma Brian F. Skinnider, Andrew J. Elia, Randy D. Gascoyne, Bruce Patterson, Lorenz Trumper, Ursula Kapp, and Tak W. Mak From the Amgen Institute and Department of Oncologic Pathology, Ontario Cancer Institute, Toronto, Canada; the Departments of Medical Biophysics and Immunology, University of Toronto, Canada; the Department of Pathology, British Columbia Cancer Agency, Vancouver, Canada; the Department of Hematology/Oncology, Georg August University, Göttingen, Germany; and the Department of Hematology/Oncology, University Medical Center, Freiburg, Germany. The unique clinicopathologic features of Hodgkin lymphoma (HL) are due to the multiple cytokines produced by its neoplastic cells, the Hodgkin and Reed-Sternberg (HRS) cells. Cytokine signaling is mediated through the signal transducer and activator of transcription (STAT) family of transcription factors. Immunoblotting and immunohistochemistry were used to examine cell lines and tissue sections derived from patients with HL and non-Hodgkin lymphoma (NHL) for expression of activated STAT proteins. Constitutive phosphorylation of STAT6 and STAT3 was common in HL. STAT6 was constitutively phosphorylated in 5 of 5 HL cell lines and in HRS cells from 25 of 32 (78%) classical HL cases. STAT3 was constitutively phosphorylated in 4 of 5 HL cell lines and in HRS cells from 27 of 31 (87%) classical HL cases. Only 4 of 24 NHL cases demonstrated constitutive STAT6 activation, whereas STAT3 activation was observed in 6 of 13 (46%) cases of B-cell NHL and 8 of 11 (73%) cases of T-cell NHL. Constitutive STAT5 phosphorylation was not a common feature of HL or NHL. STAT6 mediates signaling by interleukin 13 (IL-13), a cytokine frequently expressed by HRS cells. Antibody-mediated neutralization of IL-13 resulted in significant decreases in both cellular proliferation and levels of phosphorylated STAT6 of HL cell lines. In conclusion, constitutive STAT6 phosphorylation is a common and distinctive feature of HRS cells in classical HL, whereas STAT3 activation was regularly present in both HL and NHL. These results suggest that IL-13 signaling is largely responsible for the constitutive STAT6 activation observed in HRS cells and further implicate IL-13 as an important growth factor in classical HL. © 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: 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. Lahesmaa, and M. Boothby PARP-14, a member of the B aggressive lymphoma family, transduces survival signals in primary B cells Blood, March 12, 2009; 113(11): 2416 - 2425. [Abstract] [Full Text] [PDF] K. R. Calvo, B. Dabir, A. Kovach, C. Devor, R. Bandle, A. Bond, J. H. Shih, and E. S. Jaffe IL-4 protein expression and basal activation of Erk in vivo in follicular lymphoma Blood, November 1, 2008; 112(9): 3818 - 3826. [Abstract] [Full Text] [PDF] B. Lamprecht, S. Kreher, I. Anagnostopoulos, K. Johrens, G. Monteleone, F. Jundt, H. Stein, M. Janz, B. Dorken, and S. Mathas Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3{alpha} Blood, October 15, 2008; 112(8): 3339 - 3347. [Abstract] [Full Text] [PDF] B. H. Kim, C.-H. Yin, Q. Guo, E. A. Bach, H. Lee, C. Sandoval, S. Jayabose, A. Ulaczyk-Lesanko, D. G. Hall, and G.-H. Baeg A small-molecule compound identified through a cell-based screening inhibits JAK/STAT pathway signaling in human cancer cells Mol. Cancer Ther., September 1, 2008; 7(9): 2672 - 2680. [Abstract] [Full Text] [PDF] D. Buglio, G. V. Georgakis, S. Hanabuchi, K. Arima, N. M. Khaskhely, Y.-J. Liu, and A. Younes Vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death in Hodgkin lymphoma cell lines Blood, August 15, 2008; 112(4): 1424 - 1433. [Abstract] [Full Text] [PDF] S. J. Rodig, J. Ouyang, P. Juszczynski, T. Currie, K. Law, D. S. Neuberg, G. A. Rabinovich, M. A. Shipp, and J. L. Kutok AP1-Dependent Galectin-1 Expression Delineates Classical Hodgkin and Anaplastic Large Cell Lymphomas from Other Lymphoid Malignancies with Shared Molecular Features Clin. Cancer Res., June 1, 2008; 14(11): 3338 - 3344. [Abstract] [Full Text] [PDF] L. T. Lam, G. Wright, R. E. Davis, G. Lenz, P. Farinha, L. Dang, J. W. Chan, A. Rosenwald, R. D. Gascoyne, and L. M. Staudt Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-{kappa}B pathways in subtypes of diffuse large B-cell lymphoma Blood, April 1, 2008; 111(7): 3701 - 3713. [Abstract] [Full Text] [PDF] G Kapatai and P Murray Contribution of the Epstein Barr virus to the molecular pathogenesis of Hodgkin lymphoma J. Clin. Pathol., December 1, 2007; 60(12): 1342 - 1349. [Abstract] [Full Text] [PDF] A. Mottok, C. Renne, K. Willenbrock, M.-L. Hansmann, and A. Brauninger Somatic hypermutation of SOCS1 in lymphocyte-predominant Hodgkin lymphoma is accompanied by high JAK2 expression and activation of STAT6 Blood, November 1, 2007; 110(9): 3387 - 3390. [Abstract] [Full Text] [PDF] T. Feys, B. Poppe, K. De Preter, N. Van Roy, B. Verhasselt, P. De Paepe, A. De Paepe, and F. Speleman A detailed inventory of DNA copy number alterations in four commonly used Hodgkin's lymphoma cell lines Haematologica, July 1, 2007; 92(7): 913 - 920. [Abstract] [Full Text] [PDF] C. Aspord, A. Pedroza-Gonzalez, M. Gallegos, S. Tindle, E. C. Burton, D. Su, F. Marches, J. Banchereau, and A. K. Palucka Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development J. Exp. Med., May 14, 2007; 204(5): 1037 - 1047. [Abstract] [Full Text] [PDF] A. Sanchez-Aguilera, C. Montalban, P. de la Cueva, L. Sanchez-Verde, M. M. Morente, M. Garcia-Cosio, J. Garcia-Larana, C. Bellas, M. Provencio, V. Romagosa, et al. Tumor microenvironment and mitotic checkpoint are key factors in the outcome of classic Hodgkin lymphoma Blood, July 15, 2006; 108(2): 662 - 668. [Abstract] [Full Text] [PDF] E. Arguni, M. Arima, N. Tsuruoka, A. Sakamoto, M. Hatano, and T. Tokuhisa JunD/AP-1 and STAT3 are the major enhancer molecules for high Bcl6 expression in germinal center B cells Int. Immunol., July 1, 2006; 18(7): 1079 - 1089. [Abstract] [Full Text] [PDF] I. S. Lossos Molecular Pathogenesis of Diffuse Large B-Cell Lymphoma J. Clin. Oncol., September 10, 2005; 23(26): 6351 - 6357. [Abstract] [Full Text] [PDF] D. Re, R. Kuppers, and V. Diehl Molecular Pathogenesis of Hodgkin's Lymphoma J. Clin. Oncol., September 10, 2005; 23(26): 6379 - 6386. [Abstract] [Full Text] [PDF] D. Re, R. K. Thomas, K. Behringer, and V. Diehl From Hodgkin disease to Hodgkin lymphoma: biologic insights and therapeutic potential Blood, June 15, 2005; 105(12): 4553 - 4560. [Abstract] [Full Text] [PDF] M. Kawakami, K. Kawakami, M. Kioi, P. Leland, and R. K. Puri Hodgkin lymphoma therapy with interleukin-4 receptor-directed cytotoxin in an infiltrating animal model Blood, May 1, 2005; 105(9): 3707 - 3713. [Abstract] [Full Text] [PDF] C. Atayar, S. Poppema, T. Blokzijl, G. Harms, M. Boot, and A. van den Berg Expression of the T-Cell Transcription Factors, GATA-3 and T-bet, in the Neoplastic Cells of Hodgkin Lymphomas Am. J. Pathol., January 1, 2005; 166(1): 127 - 134. [Abstract] [Full Text] [PDF] Y. X. Zhu, S. Benn, Z. H. Li, E. Wei, E. Masih-Khan, Y. Trieu, M. Bali, C. J. McGlade, J. O. Claudio, and A. K. Stewart The SH3-SAM Adaptor HACS1 is Up-regulated in B Cell Activation Signaling Cascades J. Exp. Med., September 20, 2004; 200(6): 737 - 747. [Abstract] [Full Text] [PDF] C. Guiter, I. Dusanter-Fourt, C. Copie-Bergman, M.-L. Boulland, S. le Gouvello, P. Gaulard, K. Leroy, and F. Castellano Constitutive STAT6 activation in primary mediastinal large B-cell lymphoma Blood, July 15, 2004; 104(2): 543 - 549. [Abstract] [Full Text] [PDF] Y. Trieu, X.-Y. Wen, B. F. Skinnider, M. R. Bray, Z. Li, J. O. Claudio, E. Masih-Khan, Y.-X. Zhu, S. Trudel, J. A. McCart, et al. Soluble Interleukin-13R{alpha}2 Decoy Receptor Inhibits Hodgkin's Lymphoma Growth in Vitro and in Vivo Cancer Res., May 1, 2004; 64(9): 3271 - 3275. [Abstract] [Full Text] [PDF] J. W. Mandell Phosphorylation State-Specific Antibodies: Applications in Investigative and Diagnostic Pathology Am. J. Pathol., November 1, 2003; 163(5): 1687 - 1698. [Abstract] [Full Text] [PDF] T. F. E. Barth, J. I. Martin-Subero, S. Joos, C. K. Menz, C. Hasel, G. Mechtersheimer, R. M. Parwaresch, P. Lichter, R. Siebert, and P. Moller Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma Blood, May 1, 2003; 101(9): 3681 - 3686. [Abstract] [Full Text] [PDF] M. Benekli, M. R. Baer, H. Baumann, and M. Wetzler Signal transducer and activator of transcription proteins in leukemias Blood, April 15, 2003; 101(8): 2940 - 2954. [Abstract] [Full Text] [PDF] J. F. Garcia, F. I. Camacho, M. Morente, M. Fraga, C. Montalban, T. A. C. Bellas, A. Castano, A. Diez, T. Flores, C. Martin, et al. Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays Blood, January 15, 2003; 101(2): 681 - 689. [Abstract] [Full Text] [PDF] B. F. Skinnider and T. W. Mak The role of cytokines in classical Hodgkin lymphoma Blood, May 29, 2002; 99(12): 4283 - 4297. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020