Abstract：
Genetic alterations of the repressive ETS family transcription factor gene ETV6 are recurrent in several categories of hematopoietic malignancy, including subsets of B-cell and T-cell acute lymphoblastic leukemias (B-ALL and T-ALL), myeloid neoplasms, and mature B-cell lymphomas. ETV6 is essential for adult hematopoietic stem cells (HSCs), contributes to specific functions of some mature immune cells, and plays a key role in thrombopoiesis as demonstrated by familial ETV6 mutations associated with thrombocytopenia and predisposition to hematopoietic cancers, particularly B-ALL. ETV6 appears to have a tumor suppressor role in several hematopoietic lineages, as demonstrated by recurrent somatic loss-of-function (LoF) and putative dominant-negative alterations in leukemias and lymphomas. ETV6 rearrangements contribute to recurrent fusion oncogenes such as the B-ALL-associated transcription factor (TF) fusions ETV6::RUNX1 and PAX5::ETV6, rare drivers such as ETV6::NCOA6, and a spectrum of tyrosine kinase gene fusions encoding hyperactive signaling proteins that self-associate via the ETV6 N-terminal pointed domain. Another subset of recurrent rearrangements involving the ETV6 gene locus appear to function primarily to drive overexpression of the partner gene. This review surveys what is known about the biochemical and genome regulatory properties of ETV6 as well as our current understanding of how alterations in these functions contribute to hematopoietic and nonhematopoietic cancers.
摘要：
抑制性ETS家族转录因子基因ETV6的遗传改变在几类造血系统恶性肿瘤中反复出现，包括B细胞和T细胞急性淋巴细胞白血病（B-ALL和T-ALL）的亚群，髓样肿瘤,和成熟的B细胞淋巴瘤.ETV6对成人造血干细胞（HSC）至关重要，有助于一些成熟免疫细胞的特定功能，并在血小板生成中起关键作用，如家族性ETV6突变与血小板减少症和造血系统癌症易感性相关，尤其是B-ALL。ETV6似乎在几种造血谱系中具有肿瘤抑制作用，如白血病和淋巴瘤的复发性躯体功能丧失（LoF）和假定的显性阴性改变所证明。ETV6重排有助于复发性融合癌基因，例如B-ALL相关转录因子（TF）融合ETV6：：RUNX1和PAX5：：ETV6，罕见的驱动因素，例如ETV6：：NCOA6，以及一系列酪氨酸激酶基因融合，编码通过ETV6N末端指向结构域自我结合的高活性信号蛋白。涉及ETV6基因基因座的复发性重排的另一个子集似乎主要起驱动伴侣基因的过表达的作用。这篇综述调查了关于ETV6的生化和基因组调控特性的已知信息，以及我们目前对这些功能的改变如何导致造血和非造血癌症的理解。
