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浙江大学学报(医学版)  2015, Vol. 44 Issue (2): 197-203    DOI: 10.3785/j.issn.1008-9292.2015.03.013
Meta 分析     
DNMT3A基因突变对急性髓系白血病预后影响的meta分析
席晓平1, 曾令霞2, 余方方2, 刘华胜1
1. 西安交通大学医学部第一附属医院血液内科, 陕西 西安 710061;
2. 西安交通大学医学部公共卫生学系流行病与卫生统计学教研室, 陕西 西安 710061
Effects of DNMT3A gene mutations on prognosis of patients with acute myeloid leukemia:a meta-analysis
XI Xiao-ping1, ZENG Ling-xia2, Yu Fang-fang2, LIU Hua-sheng1
1. Department of Hematology, the First Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China;
2. Teaching and Research Section of Epidemiology and Health Statistics, Department of Public Health, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China
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摘要:

目的:采用系统评价及meta分析方法评价DNMT3A基因突变与急性髓系白血病(AML)预后间的关联。方法:采用Cochrane系统评价方法体系,计算机检索PubMed、Embase数据库、Ovid、中国知网、中国生物医学文献数据库、万方和维普等数据库收集关于DNMT3A基因突变对AML预后影响的文献,并手工检索纳入文献的参考文献。筛选相关文献,对纳入文献评价方法学质量,提取临床对照试验数据,采用Stata 11.0软件进行meta分析。结果:本研究共纳入7个临床对照试验,合计1493例研究对象。Meta分析结果显示DNMT3A基因突变患者与无DNMT3A基因突变患者比较,两组完全缓解率差异无统计学意义(OR=1.034,P=0.905,95%CI:0.596~1.796),但DNMT3A基因突变患者无病生存期(HR=2.84,P=0.002,95%CI:1.063~4.613)和总生存期(HR=1.99, P=0.000,95%CI:1.463~2.510)均较无DNMT3A基因突变患者缩短。结论:DNMT3A基因突变是AML患者预后不良的一个独立危险因素。

关键词: DNA甲基转移酶白血病,髓样,急性突变预后Meta分析(主题)    
Abstract:

Objective: To evaluate the effects of DNMT3A gene mutation on prognosis of patients with acute myeloid leukemia (AML) by a meta-analysis.Methods: Methods of Cochrane systematic review was followed by 7 databases,including PubMed, Embase, Ovid, CNKI, CBM, WanFang Data and VIP, were searched for peer-reviewed articles related to DNMT3A gene mutations and prognosis of patients with AML.Then manual retrieval was applied into literature references. After the evaluation of quality and extract of clinical trialliterature data, Stata 11.0 was employed to perform meta-analysis.Results: Seven randomized controlled trials involving 1493 cases were included in the meta-analysis. The prognosis of patients with DNMT3A mutations and without DNMT3A mutations was compared. There was no statistically significant difference in complete remission(CR) rate (OR=1.034, 95%CI:0.596~1.796, P=0.905)between two groups, but the overall survival (OS)(HR=1.990, 95%CI:1.463~2.510, P=0.000)and disease free survival (DFS)(HR= 2.840, 95%CI :1.063~4.613, P=0.002,)of patients without DNMT3A mutations were longer than those with DNMT3A mutation.Conclusion: DNMT3A gene mutation is an independent risk factor of poor prognosis of patients with acute myeloid leukemia.

Key words: Methyltransferases    Leukemia, myeloid, acute    Mutation    Prognosis    Meta-analysis as topic
收稿日期: 2014-11-05 出版日期: 2015-03-25
:  R181.3  
基金资助:

2011陕西省科学技术研究发展计划(2011K13-01-11)

通讯作者: 刘华胜(1968-),女,博士,副教授,硕士生导师,从事血液学相关临床研究;E-mail:lhs681995@126.com     E-mail: lhs681995@126.com
作者简介: 席晓平(1989-),女,硕士研究生,从事血液学相关研究;E-mail:465296876@qq.com
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引用本文:

席晓平, 曾令霞, 余方方, 刘华胜. DNMT3A基因突变对急性髓系白血病预后影响的meta分析[J]. 浙江大学学报(医学版), 2015, 44(2): 197-203.

XI Xiao-ping, ZENG Ling-xia, Yu Fang-fang, LIU Hua-sheng. Effects of DNMT3A gene mutations on prognosis of patients with acute myeloid leukemia:a meta-analysis. Journal of ZheJiang University(Medical Science), 2015, 44(2): 197-203.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2015.03.013        http://www.zjujournals.com/med/CN/Y2015/V44/I2/197

[1] DOHNER H, ESTEY E H, AMADORI S, et al. Diagnosis and management of acute myeloid leukemia in adults:recommendations from an international expert panel, on behalf of the European Leukemia Net[J]. Blood, 2010, 115(3):453-474.
[2] 陈亮,严智昌,张彦芳. 急性髓系白血病诊断的研究进展[J]. 中国冶金工业医学杂志,2012,29(04):396-398. CHEN Liang,YAN Zhi-chang,ZHANG Yan-fang.The research progress of acute myeloid leukemia diagnosis[J].Chinese Medical Journal of Metallurgical Industry,2012,29(04):396-398.(in Chinese)
[3] KELLY L M, GILLILAND D G. Genetics of myeloid leukemias[J]. Annu Rev Genomics Hum Genet, 2002, 3:179-198.
[4] MIZUNO S, CHIJIWA T, OKAMURA T, et al. Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia[J]. Blood, 2001, 97(5):1172-1179.
[5] LEY T J, DING L, WALTER M J, et al. DNMT3A mutations in acute myeloid leukemia[J]. N Engl J Med, 2010, 363(25):2424-2433.
[6] 乔纯,孙超,张苏江,等. 急性髓系白血病中DNMT3A基因突变的研究[J]. 中国实验血液学杂志,2011,19(02):303-307. QIAO Chun,SUN Chao,ZHANG Su-jiang, et al. Analysis of DNMT3A gene mutations in acute myelogenous leukemia[J]. Journal of Experimental Hematology,2011,19(02):303-307.(in Chinese)
[7] KATO N, KITAURA J, DOKI N, et al. Two types of C/EBPalpha mutations play distinct but collaborative roles in leukemogenesis:lessons from clinical data and BMT models[J]. Blood, 2011, 117(1):221-233.
[8] WELL G,SHEA B,O'CONNELL D,et al. Newcastle-ottawa quality assessment scale—cohort studies[EB/OL].[2012-06-15].http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
[9] 纪濛濛,孙自敏,刘会兰,等. 成人急性髓细胞白血病DNMT3A基因突变的检测和临床意义[J]. 安徽医药,2013,17(04):575-577. JI Meng-meng,SUN Zi-min,LIU Hui-lan,et al. The incidence of DNA methyltransferase 3 alpha(DNMT3A) gene mutation in patients with acute myeloid leukemia(AML) and its clinical significance[J]. Anhui Medical and Pharmaceutical Journal,2013,17(04):575-577.(in Chinese)
[10] 陈亚玫,鹿全意. 急性髓系白血病中的DNMT3A基因突变研究[J]. 中国实验血液学杂志,2011,19(06):1556-1560. CHEN Ya-mei,LU Quan-yi.DNMT3A gene mutations in acute myeloid leukemia—review[J]. Journal of Experimental Hematology,2011,19(06):1556-1560.(in Chinese)
[11] El GHANNAM D, TAALAB M M, GHAZY H F, et al. DNMT3A R882 mutations in patients with cytogenetically normal acute myeloid leukemia and myelodysplastic syndrome[J]. Blood Cells Mol Dis, 2014, 53(1-2):61-66.
[12] HOU H A, KUO Y Y, LIU C Y, et al. DNMT3A mutations in acute myeloid leukemia:stability during disease evolution and clinical implications[J].Blood, 2012, 119(2):559-568.
[13] YAN X J, XU J, GU Z H, et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia[J]. Nat Genet, 2011, 43(4):309-315.
[14] SHEN Y, ZHU Y M, FAN X, et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia[J]. Blood, 2011, 118(20):5593-5603.
[15] LOWENBERG B. Acute myeloid leukemia:the challenge of capturing disease variety[J]. Hematology Am Soc Hematol Educ Program,2008,2008(1):1-11.
[16] 吴皓,陈洁平. NPM1和FLT3基因同时突变影响急性髓细胞白血病患者完全缓解率的Meta分析[J]. 国际检验医学杂志,2013,34(09):1071-1073. WU Hao,CHEN Jie-ping.A Meta-analysis of effects of simultaneous mutation in NPM1 and FLT3 gene on complete remission rate patients with acute myeloid leukemia[J]. International Journal of Laboratory Medicine, 2013,34(09):1071-1073.(in Chinese)
[17] BYRD J C, MROZEK K, DODGE R K, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia:results from Cancer and Leukemia Group B (CALGB 8461) [J]. Blood, 2002, 100(13):4325-4336.
[18] SCHLENK R F, DOHNER K, KRAUTER J, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia[J].N Engl J Med, 2008, 358(18):1909-1918.
[19] LEY T J, MARDIS E R, DING L, et al. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome[J]. Nature, 2008, 456(7218):66-72.
[20] WALTER M J, DING L, SHEN D, et al. Recurrent DNMT3A mutations in patients with myelodysplastic syndromes[J]. Leukemia, 2011, 25(7):1153-1158.
[21] ABDEL-WAHAB O, PARDANANI A, RAMPAL R, et al. DNMT3A mutational analysis in primary myelofibrosis, chronic myelomonocytic leukemia and advanced phases of myeloproliferative neoplasms[J]. Leukemia, 2011, 25(7):1219-1220.

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