Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes.
Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes.
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骨髓增生异常综合征不同U2AF1突变类型的临床特征和生物学意义
DOI：
10.1002/gcc.22510
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发表时间：
2018-03
影响因子：
3.7
通讯作者：
Xiao, Zhijian
中科院分区：
文献类型：
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作者：
Li, Bing;Liu, Jinqin;Jia, Yujiao;Wang, Jingya;Xu, Zefeng;Qin, Tiejun;Shi, Zhongxun;Song, Zhen;Peng, Shuailing;Huang, Huijun;Fang, Liwei;Zhang, Hongli;Pan, Lijuan;Hu, Naibo;Qu, Shiqiang;Zhang, Yue;Wu, Jian;Liu, Na;Ru, Kun;Huang, Gang;Xiao, Zhijian
U2 AF 1突变（U2 AF 1 MT）通常发生在没有环形铁粒幼细胞的骨髓增生异常综合征（MDS）中。本研究的目的是探讨MDS中不同U2 AF 1突变类型的临床和生物学意义。我们对511例MDS患者进行了靶向基因测序。发现86例患者（17%）患有U2 AF 1 MT，这在年轻患者中更常见（P = .001），并且在相当大比例（71%）的病例中代表了祖先病变。ASXL 1 MT和分离的+8在U2 AF 1 MT阳性病例中显著富集，而TP 53 MT、SF 3B 1 MT和复杂核型与U2 AF 1 MT呈负相关。U2 AFS 34受试者富集分离的+8，与复杂核型负相关。U2 AF 1 MT与低风险和高风险MDS患者的贫血、血小板减少和生存不良显著相关。U2 AF 1 S34受试者的血小板水平<50 × 109/L的频率更高（P = 0.043），U2 AF 1 Q157/U2 AF 1 R156受试者的血红蛋白浓度<80 g/L的频率更高（P = 0.008），明显纤维化的频率更高（P = 0.049）。本研究提示U2 AF 1 MT是MDS患者最早发生的遗传事件之一，不同类型的U2 AF 1 MT具有不同的临床和生物学特征。
U2AF1 mutations (U2AF1MT) occur commonly in myelodysplastic syndromes (MDS) without ring sideroblasts. The aim of this study was to investigate the clinical and biological implications of different U2AF1 mutation types in MDS. We performed targeted gene sequencing in a cohort of 511 MDS patients. Eighty‐six patients (17%) were found to have U2AF1MT, which occurred more common in younger patients (P = .001) and represented ancestral lesions in a substantial proportion (71%) of cases. ASXL1MT and isolated +8 were significantly enriched in U2AF1MT‐positive cases, whereas TP53MT, SF3B1MT, and complex karyotypes were inversely associated with U2AF1MT. U2AFS34 subjects were enriched for isolated +8 and were inversely associated with complex karyotypes. U2AF1MT was significantly associated with anemia, thrombocytopenia, and poor survival in both lower‐risk and higher‐risk MDS. U2AF1S34 subjects had more frequently platelet levels of <50 × 109/L (P = .043) and U2AF1Q157/U2AF1R156 subjects had more frequently hemoglobin concentrations at <80 g/L (P = .008) and more often overt fibrosis (P = .049). In conclusion, our study indicates that U2AF1MT is one of the earliest genetic events in MDS patients and that different types of U2AF1MT have distinct clinical and biological characteristics.
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影响因子：
11.4
作者：
通讯作者：
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影响因子：
30.8
作者：
Makishima H;Yoshizato T;Yoshida K;Sekeres MA;Radivoyevitch T;Suzuki H;Przychodzen B;Nagata Y;Meggendorfer M;Sanada M;Okuno Y;Hirsch C;Kuzmanovic T;Sato Y;Sato-Otsubo A;LaFramboise T;Hosono N;Shiraishi Y;Chiba K;Haferlach C;Kern W;Tanaka H;Shiozawa Y;Gómez-Seguí I;Husseinzadeh HD;Thota S;Guinta KM;Dienes B;Nakamaki T;Miyawaki S;Saunthararajah Y;Chiba S;Miyano S;Shih LY;Haferlach T;Ogawa S;Maciejewski JP
通讯作者：
Maciejewski JP
影响因子：
8.8
作者：
McKerrell T;Park N;Moreno T;Grove CS;Ponstingl H;Stephens J;Understanding Society Scientific Group;Crawley C;Craig J;Scott MA;Hodkinson C;Baxter J;Rad R;Forsyth DR;Quail MA;Zeggini E;Ouwehand W;Varela I;Vassiliou GS
通讯作者：
Vassiliou GS
DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
11.4
作者：
通讯作者：
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