文章：

原发性骨髓增生异常综合征患者疾病进展过程中ASXL1突变和其他相关遗传改变的动态

Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome

原文发布日期：2014-01-17

DOI: 10.1038/bcj.2013.74

类型: Original Article

开放获取: 是

英文摘要：

Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were identified in patients with myelodysplastic syndrome (MDS), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, ASXL1 mutations were identified in 106 (22.7%) of the 466 patients with primary MDS based on the French-American-British (FAB) classification and 62 (17.1%) of the 362 patients based on the World Health Organization (WHO) classification. ASXL1 mutation was closely associated with trisomy 8 and mutations of RUNX1, EZH2, IDH, NRAS, JAK2, SETBP1 and SRSF2, but was negatively associated with SF3B1 mutation. Most ASXL1-mutated patients (85%) had concurrent other gene mutations at diagnosis. ASXL1 mutation was an independent poor prognostic factor for survival. Sequential studies showed that the original ASXL1 mutation remained unchanged at disease progression in all 32 ASXL1-mutated patients but were frequently accompanied with acquisition of mutations of other genes, including RUNX1, NRAS, KRAS, SF3B1, SETBP1 and chromosomal evolution. On the other side, among the 80 ASXL1-wild patients, only one acquired ASXL1 mutation at leukemia transformation. In conclusion, ASXL1 mutations in association with other genetic alterations may have a role in the development of MDS but contribute little to disease progression.

摘要翻译： 

最近，在骨髓增生异常综合征（MDS）患者中发现额外性梳样1（ASXL1）基因突变，但该突变与其他遗传改变的相互作用及其在疾病进展中的动态变化仍有待确定。本研究根据法美英（FAB）分类，在466例原发性MDS患者中发现106例（22.7%）存在ASXL1突变；根据世界卫生组织（WHO）分类，在362例患者中发现62例（17.1%）存在该突变。ASXL1突变与8号染色体三体及RUNX1、EZH2、IDH、NRAS、JAK2、SETBP1和SRSF2突变密切相关，但与SF3B1突变呈负相关。大多数ASXL1突变患者（85%）在诊断时伴有其他基因突变。ASXL1突变是生存期的独立不良预后因素。动态测序显示，所有32例ASXL1突变患者在疾病进展时原有突变均保持不变，但常伴随获得其他基因突变（包括RUNX1、NRAS、KRAS、SF3B1、SETBP1）及染色体演变。另一方面，在80例ASXL1野生型患者中，仅1例在白血病转化时获得ASXL1突变。结论表明，ASXL1突变与其他遗传改变共同作用可能参与MDS的发生发展，但对疾病进展影响甚微。

原文链接：

Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome