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[ABO启动子甲基化水平在成人白血病和骨髓增生异常综合征中的临床及预后意义]

[Clinical and prognostic significance of ABO promotor methylation level in adult leukemia and myelodydysplastic syndrome].

作者信息

Shao M, Tang P, Lyu X P, Yang Q K, Zhu W T, Jin H F, Wang L, Zhao X Q, Liu X, Sun L

机构信息

Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2018 Nov 1;57(11):816-823. doi: 10.3760/cma.j.issn.0578-1426.2018.11.005.

Abstract

To investigate the clinical and prognostic significance of ABO promotor methylation level in adult patients with leukemia and myelodydysplastic syndrome(MDS). ABO promoter methylation level of 182 malignant hematological disease patients and 68 normal controls were detected by bisulfite sequencing PCR.Then clinical features and outcome were compared between hypermethylation group and hypomethylation group. The median methylation rate of ABO promoter in newly diagnosed acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) were 46.98% and 11.01% respectively, which were both higher than that in controls (2.30%, 0.05). The methylation rates in remission AML and ALL were 1.58% and 2.30% respectively, which were comparable with that in normal group (0.05). As to relapse AML and ALL, methylation rates were 41.26% and 17.50% respectively, also significantly higher than that in controls (0.05).In patients with chronic myeloid leukemia (CML) chronic phase, the median methylation rate was 1.00%, which was similar to normal group. But a CML patient who transformed to ALL hadextremely high methylation rate 92.56%. The median methylation rate in patients with MDS significantly elevated as 5.81% compared with that in controls (0.05). The median overall survival (OS) of ALL and AML (non-M3) patients with hypermethylation were 12.5 months and 15.3 months, which were significantly shorter than those with hypomethylation (24.0 months and 20.0 months)(0.05).The median disease-free survival (DFS) of ALL and AML (non-M3) patients with hypermethylation were 9.9 months and 12.0 months, which were significantly shorter than those with hypomethylation (22.3 months and 18.5 months), (0.05). Multivariable analysis suggested that ABO promoter methylation level was an independent predictive factor of OS and DFS in ALL and AML (non-M(3)) patients. ABO promoter hypermethylation is closely related to genesis, development and prognosis of leukemia and MDS. Hypermethylationis related to a clinical poor prognosis compare with hypomethylation.

摘要

探讨ABO启动子甲基化水平在成人白血病和骨髓增生异常综合征(MDS)患者中的临床及预后意义。采用亚硫酸氢盐测序PCR检测182例恶性血液病患者及68例正常对照者的ABO启动子甲基化水平,然后比较高甲基化组与低甲基化组的临床特征及预后。新诊断急性髓系白血病(AML)和急性淋巴细胞白血病(ALL)患者ABO启动子的甲基化率中位数分别为46.98%和11.01%,均高于对照组(2.30%,0.05)。AML和ALL缓解期的甲基化率分别为1.58%和2.30%,与正常组相当(0.05)。复发的AML和ALL患者甲基化率分别为41.26%和17.50%,也显著高于对照组(0.05)。慢性髓系白血病(CML)慢性期患者甲基化率中位数为1.00%,与正常组相似。但1例转化为ALL的CML患者甲基化率极高,达92.56%。MDS患者甲基化率中位数显著升高至5.81%,与对照组相比差异有统计学意义(0.05)。高甲基化的ALL和AML(非M3)患者总生存期(OS)中位数分别为12.5个月和15.3个月,显著短于低甲基化患者(24.0个月和20.0个月)(0.05)。高甲基化的ALL和AML(非M3)患者无病生存期(DFS)中位数分别为9.9个月和12.0个月,显著短于低甲基化患者(22.3个月和18.5个月)(0.05)。多因素分析表明,ABO启动子甲基化水平是ALL和AML(非M3)患者OS和DFS的独立预测因素。ABO启动子高甲基化与白血病和MDS的发生、发展及预后密切相关。与低甲基化相比,高甲基化与临床预后不良相关。

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