Division of Hematology and Oncology, Department of Medicine, Northwestern University, Chicago, IL, USA.
Adv Exp Med Biol. 2024;1459:359-378. doi: 10.1007/978-3-031-62731-6_16.
ETS proto-oncogene 1 (ETS1) is a transcription factor (TF) critically involved in lymphoid cell development and function. ETS1 expression is tightly regulated throughout differentiation and activation in T-cells, natural killer (NK) cells, and B-cells. It has also been described as an oncogene in a range of solid and hematologic cancer types. Among hematologic malignancies, its role has been best studied in T-cell acute lymphoblastic leukemia (T-ALL), adult T-cell leukemia/lymphoma (ATLL), and diffuse large B-cell lymphoma (DLBCL). Aberrant expression of ETS1 in these malignancies is driven primarily by chromosomal amplification and enhancer-driven transcriptional regulation, promoting the ETS1 transcriptional program. ETS1 also facilitates aberrantly expressed or activated transcriptional complexes to drive oncogenic pathways. Collectively, ETS1 functions to regulate cell growth, differentiation, signaling, response to stimuli, and viral interactions in these malignancies. A tumor suppressor role has also been indicated for ETS1 in select lymphoma types, emphasizing the importance of cellular context in ETS1 function. Research is ongoing to further characterize the clinical implications of ETS1 dysregulation in hematologic malignancies, to further resolve binding complexes and transcriptional targets, and to identify effective therapeutic targeting approaches.
ETS 原癌基因 1（ETS1）是一种转录因子（TF），在淋巴细胞的发育和功能中起着至关重要的作用。ETS1 的表达在 T 细胞、自然杀伤（NK）细胞和 B 细胞的分化和激活过程中受到严格调控。它也被描述为多种实体瘤和血液系统恶性肿瘤的癌基因。在血液系统恶性肿瘤中，其作用在 T 细胞急性淋巴细胞白血病（T-ALL）、成人 T 细胞白血病/淋巴瘤（ATLL）和弥漫性大 B 细胞淋巴瘤（DLBCL）中研究得最为透彻。这些恶性肿瘤中 ETS1 的异常表达主要由染色体扩增和增强子驱动的转录调控驱动，促进 ETS1 转录程序。ETS1 还促进异常表达或激活的转录复合物来驱动致癌途径。总的来说，ETS1 在这些恶性肿瘤中调节细胞生长、分化、信号转导、对刺激的反应和病毒相互作用。在某些淋巴瘤类型中，ETS1 也具有肿瘤抑制作用，这强调了细胞环境对 ETS1 功能的重要性。目前正在进行研究，以进一步描述 ETS1 失调在血液系统恶性肿瘤中的临床意义，以进一步解析结合复合物和转录靶点，并确定有效的治疗靶向方法。
