Genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia in children and young adults.
Genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia in children and young adults.
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DOI：
10.3109/10428194.2015.1115041
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发表时间：
2016
影响因子：
2.6
通讯作者：
Olson TS
中科院分区：
文献类型：
--
作者：
Babushok DV;Bessler M;Olson TS
骨髓增生异常综合征（MDS）是一种克隆性血液病，其特征是无效造血、血细胞减少、发育异常和急性髓系白血病（AML）风险增加。随着临床基因检测的日益普及，越来越多的人认识到，一些遗传易感综合征可能是MDS/AML的明显新发表现的基础，特别是在儿童和年轻人中。获得性再生障碍性贫血中克隆性造血的最新发现为我们对MDS/AML易感性机制的理解增加了另一个方面。随着越来越多的易感综合征被认识到，血液学家和肿瘤学家熟悉常见的以及新出现的综合征，并有一个系统的方法来诊断和筛查高危患者人群变得越来越重要。在这里，我们提供了一个实用的算法，接近一个可疑的MDS/AML易感性的患者，并提供了一个深入的审查已建立和新兴的家族性MDS/AML综合征引起的ANKRD 26，CEBPA，DDX 41，ETV 6，GATA 2，RUNX 1，SRP 72基因突变。最后，我们讨论了获得性再生障碍性贫血的恶性转化体细胞突变的作用的最新数据，并审查MDS/AML的管理与易感综合征的患者和家庭的实际方面。
Myelodysplastic syndrome (MDS) is a clonal blood disorder characterized by ineffective hematopoiesis, cytopenias, dysplasia and an increased risk of acute myeloid leukemia (AML). With the growing availability of clinical genetic testing, there is an increasing appreciation that a number of genetic predisposition syndromes may underlie apparent de novo presentations of MDS/AML, particularly in children and young adults. Recent findings of clonal hematopoiesis in acquired aplastic anemia add another facet to our understanding of the mechanisms of MDS/AML predisposition. As more predisposition syndromes are recognized, it is becoming increasingly important for hematologists and oncologists to have familiarity with the common as well as emerging syndromes, and to have a systematic approach to diagnosis and screening of at risk patient populations. Here, we provide a practical algorithm for approaching a patient with a suspected MDS/AML predisposition, and provide an in-depth review of the established and emerging familial MDS/AML syndromes caused by mutations in the ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, SRP72 genes. Finally, we discuss recent data on the role of somatic mutations in malignant transformation in acquired aplastic anemia, and review the practical aspects of MDS/AML management in patients and families with predisposition syndromes.