TY - JOUR
T1 - GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms
AU - Geng, Xiangrong
AU - Wang, Chenguang
AU - Gao, Xin
AU - Chowdhury, Pinki
AU - Weiss, Jonathan
AU - Villegas, José A.
AU - Saed, Badeia
AU - Perera, Thilini
AU - Hu, Ying
AU - Reneau, John
AU - Sverdlov, Maria
AU - Wolfe, Ashley
AU - Brown, Noah
AU - Harms, Paul
AU - Bailey, Nathanael G.
AU - Inamdar, Kedar
AU - Hristov, Alexandra C.
AU - Tejasvi, Trilokraj
AU - Montes, Jaime
AU - Barrionuevo, Carlos
AU - Taxa, Luis
AU - Casavilca, Sandro
AU - de Pádua Covas Lage, J. Luís Alberto
AU - Culler, Hebert Fabrício
AU - Pereira, Juliana
AU - Runge, John S.
AU - Qin, Tingting
AU - Tsoi, Lam C.
AU - Hong, Hanna S.
AU - Zhang, Li
AU - Lyssiotis, Costas A.
AU - Ohe, Rintaro
AU - Toubai, Tomomi
AU - Zevallos-Morales, Alejandro
AU - Murga-Zamalloa, Carlos
AU - Wilcox, Ryan A.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85141145448&partnerID=8YFLogxK
U2 - 10.1038/s41408-022-00745-y
DO - 10.1038/s41408-022-00745-y
M3 - Artículo
C2 - 36329027
AN - SCOPUS:85141145448
SN - 2044-5385
VL - 12
JO - Blood Cancer Journal
JF - Blood Cancer Journal
IS - 11
M1 - 149
ER -