Clinical features of de novo acute myeloid leukemia with concurrent DNMT3A, FLT3 and NPM1 mutations.
Clinical features of de novo acute myeloid leukemia with concurrent DNMT3A, FLT3 and NPM1 mutations.
复制标题
DOI：
10.1186/s13045-014-0074-4
复制
发表时间：
2014-10-04
影响因子：
28.5
通讯作者：
Khoury JD
中科院分区：
文献类型：
--
作者：
Loghavi S;Zuo Z;Ravandi F;Kantarjian HM;Bueso-Ramos C;Zhang L;Singh RR;Patel KP;Medeiros LJ;Stingo F;Routbort M;Cortes J;Luthra R;Khoury JD
基于综合基因组分析，原发性急性髓性白血病（AML）合并DNMT 3A、FLT 3和NPM 1突变（AMLDNMT 3A/FLT 3/NPM 1）被认为是一个独特的AML亚群，但此类患者的临床特征尚未得到系统表征。我们评估了携带DNMT 3A、FLT 3和/或NPM 1突变的患者（n = 178）的特征，包括AMLDNMT 3A/FLT 3/NPM 1患者的索引组。AMLDNMT 3A/FLT 3/NPM 1患者（n = 35）明显年轻（中位数，56.0 vs. 62.0岁; p = 0.025），主要为女性（65.7%对46.9%; p = 0.045），骨髓原始细胞的比例更高（p < 0.001）和正常细胞遗传学（p = 0.024）。在<60岁的患者中，AMLDNMT 3A/FLT 3/NPM 1患者的无事件生存期（EFS）较短（p = 0.047）。DNMT 3A突变而非FLT 3或NPM 1突变与总生存期（OS）独立相关（p = 0.026）。在突变亚组中，AMLDNMT 3A/NPM 1患者的OS显著短于AMLFLT 3-ITD/NPM 1患者（p = 0.047），表明在NPM 1突变患者中，DNMT 3A突变的不良影响比FLT 3-ITD更明显。DNMT 3A对同时存在DNMT 3A、FLT 3和NPM 1突变的初治AML患者的临床特征和结局具有显著的显性效应。本文的在线版本（doi：10.1186/s13045-014-0074-4）包含补充材料，可供授权用户使用。
De novo acute myeloid leukemia (AML) with concurrent DNMT3A, FLT3 and NPM1 mutations (AMLDNMT3A/FLT3/NPM1) has been suggested to represent a unique AML subset on the basis of integrative genomic analysis, but the clinical features of such patients have not been characterized systematically. We assessed the features of patients (n = 178) harboring mutations in DNMT3A, FLT3 and/or NPM1, including an index group of AMLDNMT3A/FLT3/NPM1 patients. Patients with AMLDNMT3A/FLT3/NPM1 (n = 35) were significantly younger (median, 56.0 vs. 62.0 years; p = 0.025), mostly women (65.7% vs. 46.9%; p = 0.045), and presented with a higher percentage of bone marrow blasts (p < 0.001) and normal cytogenetics (p = 0.024) in comparison to patients within other mutation groups in this study. Among patients <60 years old, those with AMLDNMT3A/FLT3/NPM1 had a shorter event-free survival (EFS) (p = 0.047). DNMT3A mutations and not FLT3 or NPM1 mutations were independently associated with overall survival (OS) (p = 0.026). Within mutation subgroups, patients with AMLDNMT3A/NPM1 had a significantly shorter OS compared to those with AMLFLT3-ITD/NPM1 (p = 0.047) suggesting that the adverse impact of DNMT3A mutations is more pronounced than that of FLT3-ITD among patients with NPM1 mutation. DNMT3A has a significant dominant effect on the clinical features and outcomes of de novo AML patients with concurrent DNMT3A, FLT3 and NPM1 mutations. The online version of this article (doi:10.1186/s13045-014-0074-4) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
6.2
作者：
Chen, Weina;Konoplev, Sergej;Bueso-Ramos, Carlos E.
通讯作者：
Bueso-Ramos, Carlos E.
影响因子：
11.4
作者：
Kussick, SJ;Stirewalt, DL;Wood, BL
通讯作者：
Wood, BL
DOI：
10.1056/nejmoa1005143
发表时间：
2010-12-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ley TJ;Ding L;Walter MJ;McLellan MD;Lamprecht T;Larson DE;Kandoth C;Payton JE;Baty J;Welch J;Harris CC;Lichti CF;Townsend RR;Fulton RS;Dooling DJ;Koboldt DC;Schmidt H;Zhang Q;Osborne JR;Lin L;O'Laughlin M;McMichael JF;Delehaunty KD;McGrath SD;Fulton LA;Magrini VJ;Vickery TL;Hundal J;Cook LL;Conyers JJ;Swift GW;Reed JP;Alldredge PA;Wylie T;Walker J;Kalicki J;Watson MA;Heath S;Shannon WD;Varghese N;Nagarajan R;Westervelt P;Tomasson MH;Link DC;Graubert TA;DiPersio JF;Mardis ER;Wilson RK
通讯作者：
Wilson RK
影响因子：
20.3
作者：
Mead, Adam J.;Linch, David C.;Gale, Rosemary E.
通讯作者：
Gale, Rosemary E.
影响因子：
3.1
作者：
Markova, Jana;Michkova, Petra;Schwarz, Jiri
通讯作者：
Schwarz, Jiri