Recommended Citation
Geng X, Wang C, Gao X, Chowdhury P, Weiss J, Villegas JA, Saed B, Perera T, Hu Y, Reneau J, Sverdlov M, Wolfe A, Brown N, Harms P, Bailey NG, Inamdar K, Hristov AC, Tejasvi T, Montes J, Barrionuevo C, Taxa L, Casavilca S, de Pádua Covas Lage JLA, Culler HF, Pereira J, Runge JS, Qin T, Tsoi LC, Hong HS, Zhang L, Lyssiotis CA, Ohe R, Toubai T, Zevallos-Morales A, Murga-Zamalloa C, and Wilcox RA. GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms. Blood Cancer J 2022; 12(11):149.
Document Type
Article
Publication Date
11-4-2022
Publication Title
Blood Cancer J
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.
Medical Subject Headings
Humans; Cell Differentiation; DNA-Binding Proteins; Neoplasms; Proto-Oncogenes; T-Lymphocyte Subsets; Leukemia, Lymphoid
PubMed ID
36329027
Volume
12
Issue
11
First Page
149
Last Page
149
