High DNA methyltransferase DNMT3B levels: a poor prognostic marker in acute myeloid leukemia.
High DNA methyltransferase DNMT3B levels: a poor prognostic marker in acute myeloid leukemia.
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DOI：
10.1371/journal.pone.0051527
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Michallet M
中科院分区：
文献类型：
--
作者：
Hayette S;Thomas X;Jallades L;Chabane K;Charlot C;Tigaud I;Gazzo S;Morisset S;Cornillet-Lefebvre P;Plesa A;Huet S;Renneville A;Salles G;Nicolini FE;Magaud JP;Michallet M
最近的研究表明，DNA甲基转移酶过度表达与人类恶性肿瘤的不良预后相关，而甲基化失调仍然是定义急性髓性白血病（AML）的标志。致癌转录因子EVI 1参与甲基化失调，其过表达在预测不良结局中起主要作用。此外，AML患者中DNMT 3A突变的鉴定最近被描述为不良预后指标。为了阐明甲基化机制中这些关键因素之间的关系及其对患者结局的潜在影响，我们分析了195例初治AML患者的DNMT 3A，3B（及其非催化变体3BNC）表达及其与成人AML中其他常见预后遗传生物标志物（EVI 1，NPM 1，FLT 3 ITD/TKD和MLL）的结局和表达的相关性。DNMT 3B/3BNC的过表达（i）与较短的总生存期显著相关，和（ii）与无事件生存期和DNMT 3A表达水平显著负相关。此外，多变量分析显示，DNMT 3B/3BNC的高表达水平是统计学上显著的独立预后不良指标。这项研究代表了第一份报告，表明DNMT 3B/3BNC的过表达是AML生存不良的独立预测因子。它的量化应实施用于分层患者的治疗策略的遗传概况，并应是有用的，以确定患者谁可能受益于治疗的基础上去甲基化剂。
It has been recently shown that DNA methyl transferase overexpression is correlated with unfavourable prognosis in human malignancies while methylation deregulation remains a hallmark that defines acute myeloid leukemia (AML). The oncogenic transcription factor EVI1 is involved in methylation deregulation and its overexpression plays a major role for predicting an adverse outcome. Moreover, the identification of DNMT3A mutations in AML patients has recently been described as a poor prognostic indicator. In order to clarify relationship between these key actors in methylation mechanisms and their potential impact on patient outcomes, we analysed 195 de novo AML patients for the expression of DNMT3A, 3B (and its non-catalytic variant 3BNC) and their correlations with the outcome and the expression of other common prognostic genetic biomarkers (EVI1, NPM1, FLT3ITD/TKD and MLL) in adult AML. The overexpression of DNMT3B/3BNC is (i) significantly correlated with a shorter overall survival, and (ii) inversely significantly correlated with event-free survival and DNMT3A expression level. Moreover, multivariate analysis showed that a high expression level of DNMT3B/3BNC is statistically a significant independent poor prognostic indicator. This study represents the first report showing that the overexpression of DNMT3B/3BNC is an independent predictor of poor survival in AML. Its quantification should be implemented to the genetic profile used to stratify patients for therapeutical strategies and should be useful to identify patients who may benefit from therapy based on demethylating agents.
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影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
影响因子：
64.5
作者：
Okano, M;Bell, DW;Li, E
通讯作者：
Li, E
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：
56.9
作者：
RAZIN, A;RIGGS, AD
通讯作者：
RIGGS, AD
影响因子：
16
作者：
Palakurthy RK;Wajapeyee N;Santra MK;Gazin C;Lin L;Gobeil S;Green MR
通讯作者：
Green MR