Modelling t(8;21) acute myeloid leukaemia - What have we learned?
Modelling t(8;21) acute myeloid leukaemia - What have we learned?
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作者：
Chin PS;Bonifer C
急性髓性白血病（AML）是一种异质性的造血恶性肿瘤，由造血干细胞和祖细胞的复发性突变引起，这些突变影响表观遗传调控机制和信号分子。t（8;21）或RUNX1‐RUNX1T1易位产生RUNX1‐ETO嵌合转录因子，该转录因子为造血干细胞进一步的致癌突变事件启动，最终导致显性疾病。在体外和体内模型系统的生成方面取得了重大进展，以概括AML(8;21)，这对于了解该疾病的生物学和开发有效治疗至关重要。这篇综述提供了体内和体外模型系统的全面概述，这些模型系统被开发出来，以深入了解RUNX1 - ETO致癌活性的分子机制及其对t(8;21) AML领域知识进步的贡献。这些模型包括转基因小鼠、患者来源的异种移植物、RUNX1 - ETO转导的人祖细胞、细胞系和人胚胎干细胞模型系统，使t（8;21）成为分子水平上表征良好的AML亚型之一。t（8;21）或RUNX1‐RUNX1T1易位产生RUNX1/ETO嵌合转录因子，该转录因子与其他突变一起驱动最常见的急性髓性白血病类型之一。在这里，我们提供了体内和体外模型系统的全面概述，了解RUNX1/ETO致癌活性的分子机制。
Acute myeloid leukaemia (AML) is a heterogeneous haematopoietic malignancy caused by recurrent mutations in haematopoietic stem and progenitor cells that affect both the epigenetic regulatory machinery and signalling molecules. The t(8;21) or RUNX1‐RUNX1T1 translocation generates the RUNX1‐ETO chimeric transcription factor which primes haematopoietic stem cells for further oncogenic mutational events that in their sum cause overt disease. Significant progress has been made in generating both in vitro and in vivo model systems to recapitulate t(8;21) AML which are crucial for the understanding of the biology of the disease and the development of effective treatment. This review provides a comprehensive overview of the in vivo and in vitro model systems that were developed to gain insights into the molecular mechanisms of RUNX1‐ETO oncogenic activity and their contribution to the advancement of knowledge in the t(8;21) AML field. Such models include transgenic mice, patient‐derived xenografts, RUNX1‐ETO transduced human progenitor cells, cell lines and human embryonic stem cell model systems, making the t(8;21) as one of the well‐characterized sub‐type of AML at the molecular level. The t(8;21) or RUNX1‐RUNX1T1 translocation generates the RUNX1/ETO chimeric transcription factor which in cooperation with other mutations drives one of the most frequent types of acute myeloid leukaemia. Here, we provide a comprehensive overview of the in vivo and in vitro model systems that informed about the molecular mechanisms of RUNX1/ETO oncogenic activity.