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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1515-1523. Prepublished online as a Blood First Edition Paper on October 19, 2007; DOI 10.1182/blood-2007-04-087734. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figure All Versions of this Article: blood-2007-04-087734v1 111/3/1515    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 Ding, B. B. Articles by Ye, B. H. Search for Related Content PubMed PubMed Citation Articles by Ding, B. B. Articles by Ye, B. H. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas B. Belinda Ding1, J. Jessica Yu1, Raymond Y.-L. Yu1, Lourdes M. Mendez1, Rita Shaknovich2, Yonghui Zhang3, Giorgio Cattoretti3, and B. Hilda Ye1 1 Departments of Cell Biology and 2 Pathology, Albert Einstein College of Medicine, Bronx, NY; and 3 Department of Pathology and Institute for Cancer Genetics, Columbia University Medical Center, New York, NY Diffuse large B-cell lymphoma (DLBCL) consists of at least 2 phenotypic subtypes; that is, the germinal center B-cell–like (GCB-DLBCL) and the activated B-cell–like (ABC-DLBCL) groups. It has been shown that GCB-DLBCL responds favorably to chemotherapy and expresses high levels of BCL6, a transcription repressor known to play a causative role in lymphomagenesis. In comparison, ABC-DLBCL has lower levels of BCL6, constitutively activated nuclear factor-B, and tends to be refractory to chemotherapy. Here, we report that the STAT3 gene is a transcriptional target of BCL6. As a result, high-level STAT3 expression and activation are preferentially detected in ABC-DLBCL and BCL6-negative normal germinal center B cells. Most importantly, inactivating STAT3 by either AG490 or small interference RNA in ABC-DLBCL cells inhibits cell proliferation and triggers apoptosis. These phenotypes are accompanied by decreased expression of several known STAT3 target genes, including c-Myc, JunB, and Mcl-1, and increased expression of the cell- cycle inhibitor p27. In addition to identifying STAT3 as a novel BCL6 target gene, our results define a second oncogenic pathway, STAT3 activation, which operates in ABC-DLBCL, suggesting that STAT3 may be a new therapeutic target in these aggressive lymphomas. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. Ci, J. M. Polo, L. Cerchietti, R. Shaknovich, L. Wang, S. N. Yang, K. Ye, P. Farinha, D. E. Horsman, R. D. Gascoyne, et al. The BCL6 transcriptional program features repression of multiple oncogenes in primary B cells and is deregulated in DLBCL Blood, May 28, 2009; 113(22): 5536 - 5548. [Abstract] [Full Text] [PDF]

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