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Prepublished online as a Blood First Edition Paper on October 3, 2002; DOI 10.1182/blood-2002-07-2130. This Article Full Text (PDF) All Versions of this Article: 2002-07-2130v1 101/4/1535    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 Aoki, Y. Articles by Tosato, G. Search for Related Content PubMed PubMed Citation Articles by Aoki, Y. Articles by Tosato, G. Social Bookmarking                   What's this? Submitted July 18, 2002 Accepted September 24, 2002 Inhibition of STAT3 signaling induces apoptosis and decreases Survivin expression in primary effusion lymphoma Yoshiyasu Aoki*, Gerald M Feldman, and Giovanna Tosato Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD, USA Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MA, USA * Corresponding author; email: aokiy{at}mail.nih.gov. Despite some exciting new leads in molecular pathogenesis, AIDS-defining primary effusion lymphoma (PEL) remains a fatal malignancy. The lack of substantial progress in the management of PEL demands innovative treatment approaches. Targeting intracellular molecules critical to cell survival is one unexplored strategy for treating PEL. Here we show that inhibition of signal transducer and activator of transcription-3 (STAT3) leads to apoptosis in PEL cells. STAT3 is constitutively phosphorylated in PEL cell lines BC-1, BCBL-1 and VG-1. Transduction of dominant negative STAT3 and pharmacological STAT3 inhibition caused caspase-dependent cell death. Although STAT3 activation is known to induce expression of Bcl-2 family proteins, PEL cell apoptosis was independent of Bcl-2, Bcl-XL or Mcl-1 protein expression. Instead, STAT3 inhibition induced transcriptional repression of Survivin, a recently identified inhibitor of apoptosis. Forced overexpression of Survivin rescued VG-1 cells from apoptosis induced by STAT3 inhibition. Our findings suggest that activated STAT3 signaling directly contributes to malignant progression of PEL by preventing apoptosis, acting through the prosurvival protein Survivin. Since constitutive STAT3 activation and Survivin expression have been documented widely in different types of cancers, their linkage may extend to many malignancies and be critical to their pathogenesis. 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