학술논문
GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms
Document Type
article
Author
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 Barrionuevo; Luis 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
Source
Blood Cancer Journal, Vol 12, Iss 11, Pp 1-13 (2022)
Subject
Language
English
ISSN
2044-5385
Abstract
Abstract 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.