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

被引:79
|
作者
Chen, T-C [1 ]
Hou, H-A [1 ,2 ]
Chou, W-C [1 ,3 ]
Tang, J-L [1 ]
Kuo, Y-Y [4 ]
Chen, C-Y [1 ]
Tseng, M-H [1 ]
Huang, C-F [1 ]
Lai, Y-J [1 ]
Chiang, Y-C [1 ]
Lee, F-Y [5 ]
Liu, M-C [5 ]
Liu, C-W [3 ]
Liu, C-Y [6 ]
Yao, M. [1 ]
Huang, S-Y [1 ]
Ko, B-S [1 ]
Hsu, S-C [3 ]
Wu, S-J [1 ]
Tsay, W. [1 ]
Chen, Y-C [1 ,3 ]
Tien, H-F [1 ]
机构
[1] Natl Taiwan Univ, Coll Med, Natl Taiwan Univ Hosp, Div Hematol,Dept Internal Med, Taipei 10764, Taiwan
[2] Natl Taiwan Univ, Coll Med, Grad Inst Clin Med, Taipei 10764, Taiwan
[3] Natl Taiwan Univ, Coll Med, Natl Taiwan Univ Hosp, Dept Lab Med, Taipei 10764, Taiwan
[4] Natl Taiwan Univ, Grad Inst Oncol, Taipei 10764, Taiwan
[5] Natl Taiwan Univ, Coll Med, Natl Taiwan Univ Hosp, Dept Pathol, Taipei 10764, Taiwan
[6] Natl Taipei Univ Nursing & Hlth Sci, Dept Nursing, Biostat Consulting Lab, Taipei, Taiwan
来源
BLOOD CANCER JOURNAL | 2014年 / 4卷
关键词
ASXL1; mutation; myelodysplastic syndrome; sequential analyses; prognosis; ACUTE MYELOID-LEUKEMIA; SCORING SYSTEM; STABILITY; TRANSFORMATION; PROGNOSIS; EVOLUTION; RUNX1; JAK2; EZH2;
D O I
10.1038/bcj.2013.74
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
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.
引用
收藏
页码:e177 / e177
页数:8
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