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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3701-3713. Prepublished online as a Blood First Edition Paper on January 2, 2008; DOI 10.1182/blood-2007-09-111948. This Article Full Text Full Text (PDF) Supplemental Methods, Figures, and Tables Supplemental Tables (cont.) All Versions of this Article: blood-2007-09-111948v1 blood-2007-09-111948v2 111/7/3701    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lam, L. T. Articles by Staudt, L. M. Search for Related Content PubMed PubMed Citation Articles by Lam, L. T. Articles by Staudt, L. M. Related Collections Neoplasia Gene Expression Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-B pathways in subtypes of diffuse large B-cell lymphoma Lloyd T. Lam1, George Wright2, R. Eric Davis1, Georg Lenz1, Pedro Farinha3, Lenny Dang4, John W. Chan5, Andreas Rosenwald6, Randy D. Gascoyne3, and Louis M. Staudt1 1 Metabolism Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD; 2 Biometric Research Branch, NCI, Rockville, MD; 3 British Columbia Cancer Agency, Vancouver, BC; 4 Millennium Pharmaceuticals, Cambridge, MA; 5 Departments of Pathology and Microbiology, University of Nebraska Medical Center, Omaha; and 6 Department of Pathology, University of Würzburg, Würzburg, Germany The activated B cell–like (ABC) subgroup of diffuse large B-cell lymphoma (DLBCL) is characterized by constitutive activation of the nuclear factor-B (NF-B) pathway. In this study, we showed that the NF-B pathway induced the expression of the cytokines interleukin (IL)-6 and IL-10 in ABC DLBCL cell lines, which also have high levels of total and phosphorylated signal transducer and activator of transcription (STAT) 3 protein, suggesting autocrine signaling. Using RNA interference for STAT3, we defined a gene expression signature of IL-6 and IL-10 signaling through STAT3. Based on this signature, we constructed a molecular predictor of STAT3 signaling that defined a subset of ABC DLBCL tumors with high expression of STAT3, IL-6, and/or IL-10 and their downstream targets. Although the STAT3-high and STAT3-low subsets had equivalent expression of genes that distinguish ABC DLBCL from germinal center B cell–like DLBCL, STAT3-high ABC DLBCLs had higher expression of signatures that reflected NF-B activity, proliferation, and glycolysis. A small-molecule inhibitor of Janus kinase signaling, which blocked STAT3 signature expression, was toxic only for ABC DLBCL lines and synergized with an inhibitor of NF-B signaling. These findings suggest that the biological interplay between the STAT3 and NF-B pathways may be exploited for the treatments of a subset of ABC DLBCLs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Signaling crosstalk in DLBCL Jürgen Ruland Blood 2008 111: 3304. [Full Text] [PDF]

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