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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2924-2932. Prepublished online as a Blood First Edition Paper on December 9, 2004; DOI 10.1182/blood-2004-10-3820. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 2004-10-3820v1 105/7/2924    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 Lu, X. Articles by Lossos, I. S. Search for Related Content PubMed PubMed Citation Articles by Lu, X. Articles by Lossos, I. S. Related Collections Neoplasia Cell Adhesion and Motility Signal Transduction Gene Expression Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Distinct IL-4-induced gene expression, proliferation, and intracellular signaling in germinal center B-cell-like and activated B-cell-like diffuse large-cell lymphomas Xiaoqing Lu, Hovav Nechushtan, Feiying Ding, Manuel F. Rosado, Rakesh Singal, Ash A. Alizadeh, and Izidore S. Lossos From the Sylvester Comprehensive Cancer Center, Division of Hematology-Oncology, Department of Medicine, University of Miami, Miami, FL; and Department of Molecular and Cellular Pharmacology, University of Miami, Miami, FL. Diffuse large B-cell lymphomas (DLBCLs) can be subclassified into germinal center B-cell (GCB)-like and activated B-cell (ABC)-like tumors characterized by long and short survival, respectively. In contrast to ABC-like DLBCL, GCB-like tumors exhibit high expression of components of the interleukin 4 (IL-4) signaling pathway and of IL-4 target genes such as BCL6 and HGAL, whose high expression independently predicts better survival. These observations suggest distinct activity of the IL-4 signaling pathway in DLBCL subtypes. Herein, we demonstrate similar IL-4 expression but qualitatively different IL-4 effects on GCB-like and ABC-like DLBCL. In GCB-like DLBCL, IL-4 induces expression of its target genes, activates signal transducers and activators of transcription 6 (STAT6) signaling, and increases cell proliferation. In contrast, in the ABC-like DLBCL, IL-4 activates AKT, decreases cell proliferation by cell cycle arrest, and does not induce gene expression due to aberrant Janus kinase (JAK)-STAT6 signaling attributed to STAT6 dephosphorylation. We found distinct expression profiles of tyrosine phosphatases in DLBCL subtypes and identified putative STAT6 tyrosine phosphatases—protein tyrosine phosphatase nonreceptor type 1 (PTPN1) and PTPN2, whose expression is significantly higher in ABC-like DLBCL. These differences in tyrosine phosphatase expression might underlie distinct expression profiles of some of the IL-4 target genes and could contribute to a different clinical outcome of patients with GCB-like and ABC-like DLBCLs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Showing the way: large cell lymphoma Michael M. Quigley Blood 2005 105: 2624. [Full Text] [PDF] This article has been cited by other articles: N. Schoof, F. von Bonin, S. Zeynalova, M. Ziepert, W. Jung, M. Loeffler, M. Pfreundschuh, L. Trumper, and D. Kube Favorable impact of the interleukin-4 receptor allelic variant I75 on the survival of diffuse large B-cell lymphoma patients demonstrated in a large prospective clinical trial Ann. Onc., June 10, 2009; (2009) mdp110v1. [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] B. B. Ding, J. J. Yu, R. Y.-L. Yu, L. M. Mendez, R. Shaknovich, Y. Zhang, G. Cattoretti, and B. H. Ye Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas Blood, February 1, 2008; 111(3): 1515 - 1523. [Abstract] [Full Text] [PDF] X. Lu, J. Chen, R. Malumbres, E. Cubedo Gil, D. M. Helfman, and I. S. Lossos HGAL, a lymphoma prognostic biomarker, interacts with the cytoskeleton and mediates the effects of IL-6 on cell migration Blood, December 15, 2007; 110(13): 4268 - 4277. [Abstract] [Full Text] [PDF] S. W. Popov, G. Moldenhauer, B. Wotschke, S. Bruderlein, T. F. Barth, K. Dorsch, O. Ritz, P. Moller, and F. Leithauser Target Sequence Accessibility Limits Activation-Induced Cytidine Deaminase Activity in Primary Mediastinal B-Cell Lymphoma Cancer Res., July 15, 2007; 67(14): 6555 - 6564. [Abstract] [Full Text] [PDF] S. Goenka, S. H. Cho, and M. Boothby Collaborator of Stat6 (CoaSt6)-associated Poly(ADP-ribose) Polymerase Activity Modulates Stat6-dependent Gene Transcription J. Biol. Chem., June 29, 2007; 282(26): 18732 - 18739. [Abstract] [Full Text] [PDF] X. Lu, J. Chen, R. T. Sasmono, E. D. Hsi, K. A. Sarosiek, T. Tiganis, and I. S. Lossos T-Cell Protein Tyrosine Phosphatase, Distinctively Expressed in Activated-B-Cell-Like Diffuse Large B-Cell Lymphomas, Is the Nuclear Phosphatase of STAT6 Mol. Cell. Biol., March 15, 2007; 27(6): 2166 - 2179. [Abstract] [Full Text] [PDF] R. A. Roberts, G. Wright, A. R. Rosenwald, M. A. Jaramillo, T. M. Grogan, T. P. Miller, Y. Frutiger, W. C. Chan, R. D. Gascoyne, G. Ott, et al. Loss of major histocompatibility class II gene and protein expression in primary mediastinal large B-cell lymphoma is highly coordinated and related to poor patient survival Blood, July 1, 2006; 108(1): 311 - 318. [Abstract] [Full Text] [PDF] D. Schenten, A. Egert, M. Pasparakis, and K. Rajewsky M17, a gene specific for germinal center (GC) B cells and a prognostic marker for GC B-cell lymphomas, is dispensable for the GC reaction in mice Blood, June 15, 2006; 107(12): 4849 - 4856. [Abstract] [Full Text] [PDF] J. L. Rubenstein, J. Fridlyand, A. Shen, K. Aldape, D. Ginzinger, T. Batchelor, P. Treseler, M. Berger, M. McDermott, M. Prados, et al. Gene expression and angiotropism in primary CNS lymphoma Blood, May 1, 2006; 107(9): 3716 - 3723. [Abstract] [Full Text] [PDF] N. Kaminski and I. O. Rosas Gene expression profiling as a window into idiopathic pulmonary fibrosis pathogenesis: can we identify the right target genes? Proceedings of the ATS, January 1, 2006; 3(4): 339 - 344. [Abstract] [Full Text] [PDF] I. S. Lossos, X. Lu, and T. Tiganis PTPN2, Distinctively Expressed in GCB-Like and ABC-Like DLBCL, Is the Nuclear Phosphatase of STAT6. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 418 - 418. [Abstract] 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]

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