芪莲益髓清毒颗粒对低危骨髓增生异常综合征的疗效及其对TET2和IDH1基因的作用

Therapeutic effect of Qilian-Yisui-Qingdu granule on low-risk myelodysplastic syndrome and its effect on TET2 and IDH1 genes

目的:观察芪莲益髓清毒颗粒对低危骨髓增生异常综合征(MDS)患者的疗效,及其对甲基胞嘧啶双加氧酶2(TET2)和异柠檬酸脱氢酶1(IDH1)基因表达及甲基化的影响。方法:选取2018年01月~2019年10月就诊于山东中医药大学附属医院血液病科的IPSS-R低危MDS患者60例,采用随机数字表法将患者分为观察组和对照组,每组各30例。观察组患者给予芪莲益髓清毒颗粒及最佳的支持治疗,对照组患者仅给予最佳的支持治疗,分析两组患者治疗后的临床疗效、中医证候积分、骨髓单个核细胞TET2和IDH1基因的表达水平及甲基化情况。采用液相色谱质谱联用技术筛选芪莲益髓清毒颗粒中相关化学组分。结果:治疗后观察组治疗的总有效率显著高于对照组。观察组中医证候积分的改善优于对照组(P<0.05)。观察组和对照组治疗前TET2和IDH1 mRNA的表达水平较正常对照组降低(P<0.05);观察组治疗后的TET2和IDH1 mRNA表达水平均显著高于治疗前(P<0.05)。对照组治疗后的TET2 mRNA显著高于治疗前(P<0.05),而IDH1 mRNA表达水平则与治疗前无显著差异。治疗后,观察组TET2基因甲基化阳性率由30%下降为6.7%,IDH1基因甲基化阳性率由16.7%下降为6.7%。芪莲益髓清毒颗粒中鉴定出了与甲基化相关的21种化合物成分。结论:芪莲益髓清毒颗粒可提高支持治疗对MDS的效果,其机制可能与调控TET2和IDH1基因有关,其中包括去甲基化作用。芪莲益髓清毒颗粒治疗MDS是有效的。

AIM:To observe the curative effect of Qilian-Yisui-Qingdu granule in the treatment of low-risk myelodysplastic syndrome(MDS)and its influence on expression and methylation of methylcytosine dioxygenase 2(TET2)and isocritrate dehydrogenase 1(IDH1)genes.METHODS:The patients with IPSS-R low-risk MDS(n=60)from the Department of Hematology,Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2018 to October 2019 were randomly divided into observation group(30 cases)and control group(30 cases).The patients in observation group were given Qilian-Yisui-Qingdu granule and the best supportive treatment,while the patients in control group was only given the best supportive treatment.The curative effect,traditional chinese medicine(TCM)syndrome score,expression and methylation of TET2 and IDH1 genes in bone marrow mononuclear cells were analyzed.The related chemical components in Qilian-Yisui-Qingdu granule were screened by liquid chromatography-mass spectrometry(LC-MS).RESULTS:The total effective rate in observation group(63.33%)was significantly higher than that in control group(46.67%)after treatment.The improvement of TCM syndrome score in observation group was better than that in control group(P<0.05).The mRNA levels of TET2 and IDH1 in observation group and the control group before treatment were lower than those in normal control group(P<0.05).The mRNA levels of TET2 and IDH1 in observation group after treatment were significantly higher than those before treatment(P<0.05).The mRNA levels of TET2 control group after treatment were significantly higher than that before treatment(P<0.05).After treatment,the positive rate of TET2 methylation in observation group was decreased from 30% to 6.7%,and the positive rate of IDH1 methylation was decreased from 16.7% to 6.7%.Twenty-one compounds related to methylation were identified in Qilian-Yisui-Qingdu granule.CONCLUSION:The therapeutic effect of supportive treatment on MDS is improved by Qilian-Yisui-Qingdu granule treatment,and the mechanisms may be related to the regulation of TET2 and IDH1 genes,including demethylation.Qilian-Yisui-Qingdu granule is effective in treatment of MDS.