GATA-3 expression identifies a high-risk subset of PTCL, NOS with distinct molecular and clinical features

Tianjiao Wang, Andrew L. Feldman, David A. Wada, Ye Lu, Avery Polk, Robert Briski, Kay Ristow, Thomas M. Habermann, Dafydd Thomas, Steven C. Ziesmer, Linda E. Wellik, Thomas M. Lanigan, Thomas E. Witzig, Mark R. Pittelkow, Nathanael G. Bailey, Alexandra C. Hristov, Megan S. Lim, Stephen M. Ansell, Ryan A. Wilcox

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

The cell of origin and the tumor microenvironment's role remain elusive for the most commonperipheral T-cell lymphomas (PTCLs). As macrophages promote the growth and survival of malignant T cells and are abundant constituents of the tumor microenvironment, their functional polarization was examined in T-cell lymphoproliferative disorders. Cytokines that are abundant within the tumor microenvironment, particularly interleukin (IL)-10, were observed to promote alternative macrophage polarization. Macrophage polarization was signal transducer and activator of transcription 3 dependent and was impaired by the Janus kinase inhibitor ruxolitinib. In conventional T cells, the production of T helper (Th)2-associated cytokines and IL-10, both of which promote alternative macrophage polarization, is regulated by the T-cell transcription factor GATA-binding protein 3 (GATA-3). Therefore, its role in the T-cell lymphomas was examined. GATA-3 expression was observed in 45% of PTCLs, not otherwise specified (PTCL, NOS) and was associated with distinct molecular features, including the production of Th2-associated cytokines. In addition, GATA-3 expression identified a subset of PTCL, NOS with distinct clinical features, including inferior progression-free and overall survival. Collectively, these data suggest that further understanding the cell of origin and lymphocyte ontogeny among the T-cell lymphomas may improve our understanding of the tumor microenvironment's pathogenic role in these aggressive lymphomas.

Original languageEnglish (US)
Pages (from-to)3007-3015
Number of pages9
JournalBlood
Volume123
Issue number19
DOIs
StatePublished - May 8 2014

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Wang, T., Feldman, A. L., Wada, D. A., Lu, Y., Polk, A., Briski, R., Ristow, K., Habermann, T. M., Thomas, D., Ziesmer, S. C., Wellik, L. E., Lanigan, T. M., Witzig, T. E., Pittelkow, M. R., Bailey, N. G., Hristov, A. C., Lim, M. S., Ansell, S. M., & Wilcox, R. A. (2014). GATA-3 expression identifies a high-risk subset of PTCL, NOS with distinct molecular and clinical features. Blood, 123(19), 3007-3015. https://doi.org/10.1182/blood-2013-12-544809