Chronologic analysis of clonal evolution in acquired aplastic anemia and sMDS
Chronologic analysis of clonal evolution in acquired aplastic anemia and sMDS
复制标题
获得性再生障碍性贫血和 sMDS 克隆进化的时间分析
DOI：
10.11406/rinketsu.57.430
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Yoshizato T
中科院分区：
文献类型：
--
作者：
平野敬和・田澤晴子・藤村一郎;Akio Taniguchi;藤村一郎;Akio Taniguchi;藤村一郎;Ichiro Fujimura (藤村一郎);Akio Taniguchi;Akio Taniguchi;平野敬和・藤村一郎・田澤晴子;藤村一郎;Akio Taniguchi;藤村一郎;藤村一郎;藤村一郎;藤村一郎;Yoshizato T
获得性再生障碍性贫血（AA）是特发性骨髓衰竭的一种原型，它是由免疫介导的造血祖细胞破坏引起的，但也以频繁进化为克隆性髓系疾病为特征，如骨髓增生异常综合征或急性髓系白血病。然而，克隆的时间行为及其与骨髓增生异常综合征或急性髓系白血病的联系尚未得到充分探讨。为了确定AA的克隆性及其时间顺序行为，我们对AA患者进行了靶向测序（N= 439）。在三分之一的病例中检测到体细胞突变。DNMT3A突变最为常见，其次是BCOR、PIGA和ASXL1。突变的发生率随着年龄的增长而增加。DNMT3A和ASXL1的克隆大小倾向于增加，而BCOR和PIGA的克隆大小倾向于减少或保持稳定。PIGA、BCOR和BCORL1突变与免疫抑制治疗的更好反应和更有利的生存相关。另一方面，其他突变与更糟糕的结果相关。克隆的时间动态表现出显著的可变性，并不一定与预后相关。
Acquired aplastic anemia (AA) is a prototype of idiopathic bone marrow failure, which is caused by immune-mediated destruction of hematopoietic progenitors but is also characterized by frequent evolution to clonal myeloid disorders, such as myelodysplastic syndromes or acute myeloid leukemia. However, the chronological behavior of the clonality and its link to myelodysplastic syndrome or acute myeloid leukemia has not been fully explored. To define the clonality and its chronological behavior in AA, we performed targeted sequencing (N= 439) in cases with AA. Somatic mutations were detected in 1/3 of our cases. Mutations were most frequently found in DNMT3A, followed by BCOR, PIGA and ASXL1. The prevalence of mutations increased with age. The clone sizes in DNMT3A and ASXL1 were prone to increase, whereas those of BCOR and PIGA were more likely to decrease or remain stable. Mutations in PIGA, BCOR and BCORL1 correlated with a better response to immunosuppressive therapy and more favorable survival. On the other hand, other mutations were associated with worse outcomes. The chronological dynamics of clonality showed marked variability and were not necessarily associated with prognosis.