文章：

GATA-3是T细胞淋巴增殖性肿瘤中的一种原癌基因

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

原文发布日期：2022-11-04

DOI: 10.1038/s41408-022-00745-y

类型: Article

开放获取: 是

英文摘要：

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.
 

摘要翻译： 

起源于胸腺T细胞祖细胞及胸腺后成熟T细胞亚群的肿瘤在淋巴细胞增殖性肿瘤中占少数。这些T细胞来源的肿瘤虽在分子和遗传层面具有异质性，但都利用了正常T细胞生物学中至关重要的转录因子和信号通路，包括参与抗原、共刺激及细胞因子受体信号传导的途径。转录因子GATA-3调控未成熟与成熟T细胞的生长增殖，近期研究发现其与T细胞肿瘤的发生相关，包括西方世界最常见的成熟T细胞淋巴瘤。本文揭示GATA-3在各类T细胞肿瘤（包括来源于T细胞祖细胞及其成熟子代细胞的肿瘤）中均发挥原癌基因作用，并进一步明确了GATA-3依赖的转录调控程序，其中包含可成为治疗靶点的基因产物。研究还发现p300依赖性乙酰化通过减弱DNA结合来调控GATA-3介导的转录，这一发现具有新的治疗意义。鉴于多数罹患GATA-3驱动型T细胞肿瘤的患者会在确诊后数年内死亡，这些研究成果为改善此类患者的预后提供了新的机遇。

原文链接：

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