Saida Satoshi
Oncogenesis and Development Section, National Human Genome Research Institute, National Institutes of Health, Bldg 49, RM 4A25 49 Convent DR, Bethesda, MD, 20892, USA.
Department of Pediatrics, Kyoto University Hospital, Kyoto, Japan.
Curr Treat Options Oncol. 2017 Jul;18(7):41. doi: 10.1007/s11864-017-0485-x.
Leukemia is the most common pediatric cancer and accounts for approximately one third of childhood malignancies. There are germline genetic alterations that significantly increase the risk of developing hematopoietic malignancies in childhood. In this review, we describe a number of these hereditary disorders and their clinical features. These predispositions to cancer syndromes can be attributed to DNA repair/genetic instability, RAS pathway dysfunction, bone marrow failure, telomeropathies, immunodeficiencies, transcription factor abnormalities, pure familial leukemia, and aneuploidy. We focus especially on acute myeloid leukemia associated with Down syndrome, but also include other hereditary syndromes in this review. Recent advances in high-throughput genotyping technology have identified new genetic variations prone to human leukemia. Understanding of the mechanism of leukemia development in these hereditary syndromes allows us to gain insight into leukemogenesis in general and suggests therapeutic strategies based on these findings.
白血病是最常见的儿童癌症，约占儿童恶性肿瘤的三分之一。存在一些种系基因改变，可显著增加儿童发生造血系统恶性肿瘤的风险。在本综述中，我们描述了其中一些遗传性疾病及其临床特征。这些癌症综合征的易感性可归因于DNA修复/基因不稳定、RAS信号通路功能障碍、骨髓衰竭、端粒病、免疫缺陷、转录因子异常、纯合家族性白血病和非整倍体。我们特别关注与唐氏综合征相关的急性髓系白血病，但本综述也包括其他遗传性综合征。高通量基因分型技术的最新进展已鉴定出易患人类白血病的新基因变异。了解这些遗传性综合征中白血病的发生机制，有助于我们全面深入了解白血病的发病过程，并根据这些发现提出治疗策略。
