GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms

Xiangrong Geng, Chenguang Wang, Xin Gao, Pinki Chowdhury, Jonathan Weiss, José A. Villegas, Badeia Saed, Thilini Perera, Ying Hu, John Reneau, Maria Sverdlov, Ashley Wolfe, Noah Brown, Paul Harms, Nathanael G. Bailey, Kedar Inamdar, Alexandra C. Hristov, Trilokraj Tejasvi, Jaime Montes, Carlos BarrionuevoLuis Taxa, Sandro Casavilca, J. Luís Alberto de Pádua Covas Lage, Hebert Fabrício Culler, Juliana Pereira, John S. Runge, Tingting Qin, Lam C. Tsoi, Hanna S. Hong, Li Zhang, Costas A. Lyssiotis, Rintaro Ohe, Tomomi Toubai, Alejandro Zevallos-Morales, Carlos Murga-Zamalloa, Ryan A. Wilcox

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

Resumen

Neoplasms 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.

Idioma originalInglés
Número de artículo149
PublicaciónBlood Cancer Journal
Volumen12
N.º11
DOI
EstadoPublicada - nov. 2022
Publicado de forma externa

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© 2022, The Author(s).

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