成人急性髓系白血病中DNMT3A的表达及其意义

doi:10.3969/j.issn.1673-8640.2016.02.002

摘要/Abstract

摘要：

目的比较DNA甲基化转移酶（DNMT）3A在初发成人急性髓系白血病（AML）与正常对照者间的差异,探讨DNMT3A表达与法美英（FAB）分型、核磷酸化蛋白1（NPM1）、FMS样的酪氨酸激酶3（FLT3）以及c-KIT之间的关系。方法运用荧光定量聚合酶链反应（PCR）检测78例初发成人AML患者和10例对照者的DNMT3A表达水平。结果初发成人AML患者DNMT3A表达低于对照组（P=0.002）。FAB分型与DNMT3A表达量具有相关性（r=0.342,P=0.002）。M3与M5患者间DNMT3A表达具有明显差异（P=0.001）。NPM1突变阳性患者DNMT3A表达高于野生型患者（P=0.001）。NPM1⁺/FLT3-内部串联重复（ITD）^-患者DNMT3A表达高于其他类型患者（NPM1⁺/FLT3-ITD⁺、NPM1^-/FLT3-ITD⁺、NPM1^-/FLT3-ITD^-）（P=0.007）。c-KIT突变阳性患者DNMT3A表达显著低于野生型患者（P=0.007）。DNMT3A表达量与骨髓涂片中原始细胞比例无相关（r=0.208,P=0.078）。DNMT3A表达在核型正常与异常患者（P=0.214）,FLT3突变阳性患者与野生型患者间（P=0.397）差异无统计学意义。结论 DNMT3A在初发成人AML中表达降低,且在FAB各型间存在差异。DNMT3A低表达与NPM1野生型、c-KIT基因突变的协同作用可能在AML发病中起重要作用。

关键词: DNA甲基化转移酶3A, 急性髓系白血病, 荧光定量聚合酶链反应, 基因突变

Abstract:

Objective To compare the expression difference of DNA methyltransferase（DNMT）3A between adult patients with de novo acute myeloid leukemia （AML） and healthy controls,and to investigate the relationships of DNMT3A expression with French-American-British（FAB）classification, nucleophosmin 1（NPM1）, FMS-like tyrosine kinase 3（FLT3） and c-KIT. Methods The expressions of DNMT3Awere determined by fluorescence quantitation polymerase chain reaction （PCR） in 78 de novo AML adult patients and 10 healthy controls. Results Compared with healthy control group,the expression ofDNMT3A decreased in de novo AML adult group （P=0.002）. There was a relationship between FAB classification and DNMT3A expression （r=0.342,P=0.002）. M3 and M5 patients showed significant difference in the expression of DNMT3A （P=0.001）. The expression of DNMT3A was significantly higher in NPM1 mutation patients than in non-NPM1 mutation patients （P=0.001）. The DNMT3Aexpression increased in NPM1⁺/FLT3-internal tandem duplication （ITD）^- patients compared with other patients （NPM1⁺/FLT3-ITD⁺,NPM1^-/FLT3-ITD⁺ and NPM1^-/FLT3-ITD^-）（P=0.007）. The expression of DNMT3A in patients with c-KIT mutation was lower significantly than that in patients without c-KIT mutation （P=0.007）. There was no correlation between DNMT3A expression and blast cell proportion in bone marrow smear （r=0.208,P=0.078）. There was no statistical significance for DNMT3A expression between patients with and without abnormal karyotype （P=0.214）. No statistical significance was found in DNMT3A expression between patients with and without FLT3 mutation （P=0.397）. Conclusions In adult patients with de novo AML,DNMT3A expression is down regulated and has difference with FAB classification. The low expression of DNMT3A may play an important role in the pathogenesis of AML by co-operating with NPM1 wild type and c-KIT mutation.

Key words: DNA methyltransferase 3A, Acute myeloid leukemia, Fluorescence quantitation polymerase chain reaction, Gene mutation

中图分类号:

R446.11

王小蕊, 杨一宁, 秦尤文. 成人急性髓系白血病中DNMT3A的表达及其意义[J]. 检验医学, 2016, 31(2): 87-90.

WANG Xiaorui, YANG Yining, QIN Youwen. Expression and its significance of DNMT3A in adult patients with acute myeloid leukemia[J]. Laboratory Medicine, 2016, 31(2): 87-90.

图/表 2

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组别	例数	DNMT3A/CCND2中位值	DNMT3A/CCND2范围	P值
FAB分型
M1	2	0.28	0.20~0.36	—
M2	19	0.44	0.11~2.11	0.002
M3	11	0.27	0.09~0.69	<0.000 1
M4	24	0.40	0.16~2.11	0.003
M5	22	0.71	0.06~2.72	0.24
对照组	10	0.93	0.56~1.35	—

组别	例数	DNMT3A/CCND2中位值	DNMT3A/CCND2范围	P值
FAB分型
M1	2	0.28	0.20~0.36	—
M2	19	0.44	0.11~2.11	0.002
M3	11	0.27	0.09~0.69	<0.000 1
M4	24	0.40	0.16~2.11	0.003
M5	22	0.71	0.06~2.72	0.24
对照组	10	0.93	0.56~1.35	—