Frequent ASXL1 mutations in children and young adults with chronic myeloid leukemia
Frequent ASXL1 mutations in children and young adults with chronic myeloid leukemia
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DOI：
10.1038/s41375-018-0157-2
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发表时间：
2018-09-01
期刊：
影响因子：
11.4
通讯作者：
Gruhn, Bernd
中科院分区：
文献类型：
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作者：
Ernst, Thomas;Busch, Melinda;Gruhn, Bernd
在过去的十年中，在骨髓恶性肿瘤中发现了大量影响多种途径的体细胞突变，其频率和组合不同，与不同的疾病实体重叠[1]。最初，在基因中发现了畸变，这些基因通过改变信号通路和关键转录靶点的表达来赋予生长优势。随着时间的推移，其他途径，如表观遗传修饰，RNA剪接，和粘蛋白复合物被发现参与髓系白血病的发生。最近对大规模人群的全外显子组筛查显示，许多这些畸变也可以在健康的老年人中发现[2-4]。在65岁以上的人群中观察到10%的克隆性造血与体细胞突变，但在50岁以下的人群中仅观察到1%[2]。大多数变异发生在先前与骨髓癌有关的基因中，最常见的是DNMT 3A，
In the last decade a large number of somatic mutations affecting multiple pathways have been identified in myeloid malignancies with varying frequencies and combinations that overlap the different disease entities [1]. Initially, aberrations were discovered in genes that confer a growth advantage by altering signaling pathways and expression of key transcriptional targets. Over time, additional pathways such as epigenetic modification, RNA splicing, and the cohesin complex were found to be involved in myeloid leukemogenesis. Recent whole-exome screenings of large populations have revealed that many of these aberrations can also be found in healthy elderly people [2–4]. Clonal hematopoiesis with somatic mutations was observed in 10% of the population above 65 years of age, but in only 1% of people younger than 50 years of age [2]. The majority of the variants occurred in genes that have previously been implicated in myeloid cancers, most frequently DNMT3A,