AML和ALL患者骨髓DNMT1,SFRP1基因甲基化及其与临床病理特征和预后相关性研究  

Methylation of DNMT1 and SFRP1 Gene in Bone Marrow and Its Correlation with Clinicopathological Features and Prognosis in Patients with AML and ALL

作　　者：陈莉[1] 张丛丛[1] 李青山[2] 索晓慧 吉慧娟 刘洪峰[1] CHEN Li;ZHANG Cong-cong;LI Qing-shan;SUO Xiao-hui;JI Hui-juan;LIU Hong-feng(Department of Hematology,Handan Central Hospital,Hebei Handan 056001,China;Department of Orthopedics,Handan Central Hospital,Hebei Handan 056001,China)

机构地区：[1]邯郸市中心医院血液内科,河北邯郸056001 [2]邯郸市中心医院骨科,河北邯郸056001

出　　处：《现代检验医学杂志》2022年第6期7-13,共7页Journal of Modern Laboratory Medicine

基　　金：河北省医学科学研究科研项目(1723021282)。

摘　　要：目的检测急性髓系白血病(acute myeloid leukemia,AML)和急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)患者骨髓中DNA甲基化转移酶1(DNA methyltransferase 1,DNMT1)、分泌型卷曲相关蛋白1(secreted frizzled related protein 1,SFRP1)基因甲基化及mRNA表达水平,探讨其与临床病理特征和预后的关系。方法根据FBA(French-American-British classification systems;法-美-英分型系统)标准选取2019年11月~2020年11月于邯郸市中心医院新诊断的急性白血病患者70例,其中AML 50例和ALL 20例;另选取65例非恶性血液病患者作为正常对照组。用甲基化特异性聚合酶链式反应(methylation-specific PCR,MSP)检测所有研究对象骨髓标本中DNMT1和SFRP1基因甲基化状态,并分析两基因甲基化与AML和ALL患者临床参数之间的关系;用实时定量PCR检测所有研究对象化疗前和化疗缓解后骨髓标本中DNMT1,SFRP1和β-catenin mRNA表达;Pearson相关分析明确DNMT1,SFRP1和β-catenin mRNA水平之间的相关性;对所有患者进行随访,比较DNMT1和SFRP1基因甲基化与预后的关系。结果AML和ALL患者中DNMT1基因甲基化发生率分别为26.0%和25.0%,较对照组(73.8%)显著下降(χ^(2)=47.683,P<0.001);SFRP1基因甲基化发生率分别为78.0%和85.0%,较正常对照组(18.5%)显著增加(χ^(2)=55.265,P<0.001),差异均有统计学意义。AML组DNMT1基因甲基化与WBC水平、遗传学预后分组有明显相关性(χ^(2)=6.524,5.732,均P<0.001);SFRP1基因甲基化与WBC水平、BM水平和遗传学预后分组有明显相关性(χ^(2)=8.115,5.395,5.060,均P<0.05)。ALL组DNMT1基因甲基化只与遗传学预后分组有关(χ^(2)=4.802,P<0.05);SFRP1基因甲基化与WBC水平、遗传学预后分组有明显相关性(χ^(2)=4.920,5.115,均P<0.05)。与对照组相比,AML和ALL患者化疗前DNMT1和β-catenin mRNA表达均显著升高(t=4.807~10.456,均P<0.05),SFRP1表达显著下降(t=24.791,12.069,均P<0.05)。与化疗前相比,AML和ALL患者化疗后DNMT1和�Objective To detect the levels of DNA methyltransferase 1(DNMT1)secretory frizzled related protein 1(SFRP1)gene methylation and mRNA expression in bone marrow of patients with acute myeloid leukemia(AML)and acute lymphoblastic leukemia(ALL),and explore their relationship with clinicopathological characteristics and prognosis.Methods From November 2019 to November 2020,70 patients with newly diagnosed acute leukemia in Handan Central Hospital were selected according to FBA(French-American-British classification systems)criteria,including 50 patients with AML and 20 patients with ALL.Another 65 patients with non-malignant hematologic diseases were selected as normal control group.Methylation-specific PCR(MSP)was used to detect the methylation status of DNMT1 and SFRP1 genes in bone marrow samples of ALL subjects,and the relationship between methylation of DNMT1 and SFRP1 genes and clinical parameters of AML and ALL patients was analyzed.Real time quantitative PCR was used to detect DNMT1,SFRP1 andβ-catenin mRNA expression in all subjects before chemotherapy and after chemotherapy.Pearson correlation analysis identifies correlations between DNMT1,SFRP1 andβ-catenin mRNA levels.All patients were followed up to compare the relationship between DNMT1 and SFRP1 methylation and prognosis.Results The incidence of DNMT1 gene methylation in AML and ALL patients were 26.0%and 25.0%,respectively,which was significantly lower than that in the control group(73.8%)(χ^(2)=47.683,P<0.001).The methylation rates of SFRP1 gene were 78.0%and 85.0%,respectively,which were significantly higher than those of normal control group(18.5%)(χ^(2)=55.265,P<0.001),and the differences were statistically significant,respectively.There was significant correlation between DNMT1 methylation and WBC level in AML group and genetic prognosis group(χ^(2)=6.524,5.732,all P<0.001).The methylation of SFRP1 was significantly correlated with WBC level,BM level and genetic prognosis group(χ^(2)=8.115,5.395,5.060,all P<0.05).DNMT1 gene methylation was on

关 键 词：恶性血液病 DNA甲基化转移酶1(DNMT1) 分泌型卷曲相关蛋白1(SFRP1) 基因甲基化 

分 类 号：R557[医药卫生—血液循环系统疾病] R446.11[医药卫生—内科学]