Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas

B. Belinda Ding, J. Jessica Yu, Raymond Y.L. Yu, Lourdes M. Mendez, Rita Shaknovich, Yonghui Zhang, Giorgio Cattoretti, B. Hilda Ye

Research output: Contribution to journalArticle

206 Scopus citations


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, ABCDLBCL has lower levels of BCL6, constitutively activated nuclear factor-κB, 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 ABCDLBCL 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 ABCDLBCL, suggesting that STAT3 may be a new therapeutic target in these aggressive lymphomas.

Original languageEnglish (US)
Pages (from-to)1515-1523
Number of pages9
Issue number3
StatePublished - Feb 12 2008


ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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