Dynamics of clonal evolution in myelodysplastic syndromes.
Dynamics of clonal evolution in myelodysplastic syndromes.
复制标题
DOI：
10.1038/ng.3742
复制
发表时间：
2017-03
期刊：
影响因子：
30.8
通讯作者：
Maciejewski JP
中科院分区：
文献类型：
--
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
为了阐明突变在骨髓增生异常综合征（MDS）中的不同作用，我们使用全外显子组和/或靶向测序对699例患者的克隆动力学进行了研究，其中122例进行了纵向分析。包括以前报告的结果，我们评估了总共2,250例患者的突变富集模式。在进展过程中，突变的数量，它们的多样性和克隆大小增加，改变经常出现在显性克隆中，有或没有它们的清扫以前的克隆。在继发性急性髓性白血病（sAML;与高危MDS相比）中富集的FLT 3、PTPN 11、WT 1、IDH 1、NPM 1、IDH 2和NRAS突变（1型）倾向于新获得，并且与更快的sAML进展和更短的总生存时间相关。与低风险MDS相比，TP 53、GATA 2、KRAS、RUNX 1、STAG 2、ASXL 1、ZRSR 2和TET 2突变（2型）在高风险MDS中显著富集，对sAML进展和总生存期的影响弱于1型突变。1型和2型突变的不同作用表明它们在疾病监测中的潜在效用。
To elucidate differential roles of mutations in myelodysplastic syndromes (MDS), we investigated clonal dynamics using whole-exome and/or targeted sequencing of 699 patients, of whom 122 were analyzed longitudinally. Including the results from previous reports, we assessed a total of 2,250 patients for mutational enrichment patterns. During progression, the number of mutations, their diversity and clone sizes increased, with alterations frequently present in dominant clones with or without their sweeping previous clones. Enriched in secondary acute myeloid leukemia (sAML; in comparison to high-risk MDS), FLT3, PTPN11, WT1, IDH1, NPM1, IDH2 and NRAS mutations (type 1) tended to be newly acquired, and were associated with faster sAML progression and a shorter overall survival time. Significantly enriched in high-risk MDS (in comparison to low-risk MDS), TP53, GATA2, KRAS, RUNX1, STAG2, ASXL1, ZRSR2 and TET2 mutations (type 2) had a weaker impact on sAML progression and overall survival than type-1 mutations. The distinct roles of type-1 and type-2 mutations suggest their potential utility in disease monitoring.
登录
查看更多内容
影响因子：
30.8
作者：
Busque L;Patel JP;Figueroa ME;Vasanthakumar A;Provost S;Hamilou Z;Mollica L;Li J;Viale A;Heguy A;Hassimi M;Socci N;Bhatt PK;Gonen M;Mason CE;Melnick A;Godley LA;Brennan CW;Abdel-Wahab O;Levine RL
通讯作者：
Levine RL
影响因子：
11.4
作者：
通讯作者：
--
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：
--
影响因子：
20.3
作者：
Grossmann, Vera;Tiacci, Enrico;Falini, Brunangelo
通讯作者：
Falini, Brunangelo