文章：

急性白血病和髓系肿瘤的种系易感性研究进展

Advances in germline predisposition to acute leukaemias and myeloid neoplasms

原文发布日期：2020-12-16

DOI: 10.1038/s41568-020-00315-z

类型: Review Article

开放获取: 否

英文摘要：

Although much work has focused on the elucidation of somatic alterations that drive the development of acute leukaemias and other haematopoietic diseases, it has become increasingly recognized that germline mutations are common in many of these neoplasms. In this Review, we highlight the different genetic pathways impacted by germline mutations that can ultimately lead to the development of familial and sporadic haematological malignancies, including acute lymphoblastic leukaemia, acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). Many of the genes disrupted by somatic mutations in these diseases (for example, TP53, RUNX1, IKZF1 and ETV6) are the same as those that harbour germline mutations in children and adolescents who develop these malignancies. Moreover, the presumption that familial leukaemias only present in childhood is no longer true, in large part due to the numerous studies demonstrating germline DDX41 mutations in adults with MDS and AML. Lastly, we highlight how different cooperating events can influence the ultimate phenotype in these different familial leukaemia syndromes.

摘要翻译： 

尽管大量研究致力于阐明驱动急性白血病和其他造血系统疾病发展的体细胞突变，但人们逐渐认识到种系突变在许多此类肿瘤中其实相当常见。在本综述中，我们重点探讨了受种系突变影响的不同遗传通路如何最终导致家族性和散发性血液恶性肿瘤的发生，包括急性淋巴细胞白血病、急性髓系白血病（AML）和骨髓增生异常综合征（MDS）。这些疾病中因体细胞突变而失调的许多基因（如TP53、RUNX1、IKZF1和ETV6），与罹患这些恶性肿瘤的儿童和青少年携带种系突变的基因相同。此外，认为家族性白血病仅见于儿童期的观点已不再成立，这主要得益于多项研究证实成年MDS和AML患者存在种系DDX41突变。最后，我们重点阐述了不同的协同事件如何影响这些不同家族性白血病综合征的最终表型。

原文链接：

Advances in germline predisposition to acute leukaemias and myeloid neoplasms