GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms
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Published:2022-11-04
Issue:11
Volume:12
Page:
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ISSN:2044-5385
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Container-title:Blood Cancer Journal
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language:en
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Short-container-title:Blood Cancer J.
Author:
Geng XiangrongORCID, Wang ChenguangORCID, Gao Xin, Chowdhury PinkiORCID, Weiss JonathanORCID, Villegas José A.ORCID, Saed BadeiaORCID, Perera ThiliniORCID, Hu Ying, Reneau John, Sverdlov Maria, Wolfe AshleyORCID, Brown Noah, Harms Paul, Bailey Nathanael G.ORCID, Inamdar KedarORCID, Hristov Alexandra C., Tejasvi Trilokraj, Montes Jaime, Barrionuevo CarlosORCID, Taxa LuisORCID, Casavilca SandroORCID, de Pádua Covas Lage J. Luís AlbertoORCID, Culler Hebert FabrícioORCID, Pereira JulianaORCID, Runge John S.ORCID, Qin Tingting, Tsoi Lam C., Hong Hanna S.ORCID, Zhang Li, Lyssiotis Costas A., Ohe RintaroORCID, Toubai TomomiORCID, Zevallos-Morales AlejandroORCID, Murga-Zamalloa CarlosORCID, Wilcox Ryan A.ORCID
Abstract
AbstractNeoplasms originating from thymic T-cell progenitors and post-thymic mature T-cell subsets account for a minority of lymphoproliferative neoplasms. These T-cell derived neoplasms, while molecularly and genetically heterogeneous, exploit transcription factors and signaling pathways that are critically important in normal T-cell biology, including those implicated in antigen-, costimulatory-, and cytokine-receptor signaling. The transcription factor GATA-3 regulates the growth and proliferation of both immature and mature T cells and has recently been implicated in T-cell neoplasms, including the most common mature T-cell lymphoma observed in much of the Western world. Here we show that GATA-3 is a proto-oncogene across the spectrum of T-cell neoplasms, including those derived from T-cell progenitors and their mature progeny, and further define the transcriptional programs that are GATA-3 dependent, which include therapeutically targetable gene products. The discovery that p300-dependent acetylation regulates GATA-3 mediated transcription by attenuating DNA binding has novel therapeutic implications. As most patients afflicted with GATA-3 driven T-cell neoplasms will succumb to their disease within a few years of diagnosis, these findings suggest opportunities to improve outcomes for these patients.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases U.S. Department of Health & Human Services | NIH | National Cancer Institute
Publisher
Springer Science and Business Media LLC
Subject
Oncology,Hematology
Reference63 articles.
1. Wang T, Feldman AL, Wada DA, Lu Y, Polk A, Briski R, et al. GATA-3 expression identifies a high-risk subset of PTCL, NOS with distinct molecular and clinical features. Blood 2014;123:3007–15. 2. Iqbal J, Wright G, Wang C, Rosenwald A, Gascoyne RD, Weisenburger DD, et al. Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. Blood 2014;123:2915–23. 3. Wang T, Lu Y, Polk A, Chowdhury P, Zamalloa CM, Fujiwara H, et al. T-cell receptor signaling activates an ITK/NF-kappaB/GATA-3 axis in T-cell lymphomas facilitating resistance to chemotherapy. Clin Cancer Res. 2017;23:2506–15. 4. Chen Y, Bates DL, Dey R, Chen PH, Machado AC, Laird-Offringa IA, et al. DNA binding by GATA transcription factor suggests mechanisms of DNA looping and long-range gene regulation. Cell Rep. 2012;2:1197–206. 5. Bates DL, Chen Y, Kim G, Guo L, Chen L. Crystal structures of multiple GATA zinc fingers bound to DNA reveal new insights into DNA recognition and self-association by GATA. J Mol Biol. 2008;381:1292–306.
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