TY - JOUR
T1 - GATA-3 expression identifies a high-risk subset of PTCL, NOS with distinct molecular and clinical features
AU - Wang, Tianjiao
AU - Feldman, Andrew L.
AU - Wada, David A.
AU - Lu, Ye
AU - Polk, Avery
AU - Briski, Robert
AU - Ristow, Kay
AU - Habermann, Thomas M.
AU - Thomas, Dafydd
AU - Ziesmer, Steven C.
AU - Wellik, Linda E.
AU - Lanigan, Thomas M.
AU - Witzig, Thomas E.
AU - Pittelkow, Mark R.
AU - Bailey, Nathanael G.
AU - Hristov, Alexandra C.
AU - Lim, Megan S.
AU - Ansell, Stephen M.
AU - Wilcox, Ryan A.
PY - 2014/5/8
Y1 - 2014/5/8
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2013-12-544809
DO - 10.1182/blood-2013-12-544809
M3 - Article
C2 - 24497534
AN - SCOPUS:84900402661
SN - 0006-4971
VL - 123
SP - 3007
EP - 3015
JO - Blood
JF - Blood
IS - 19
ER -