Traditional Chinese Medicine Containing Arsenic Treated MDS Patients Effectively through Regulating Aberrant Hypomethylation
Traditional Chinese Medicine Containing Arsenic Treated MDS Patients Effectively through Regulating Aberrant Hypomethylation
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含砷中药通过调节异常低甲基化有效治疗MDS患者
DOI：
10.1155/2020/7469809
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发表时间：
2020-03-09
影响因子：
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通讯作者：
Xu, Feng-qin
中科院分区：
文献类型：
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作者：
Zhou, Qing-bing;Zhu, Qian-zhe;Xu, Feng-qin
异常的高甲基化和低甲基化在骨髓增生异常综合征（MDS）中均起重要作用。以超甲基化为靶点的去甲基化药物已被用于MDS的治疗，但治疗效果有限。为提高MDS的临床疗效，需要寻找新的DNA低甲基化靶向治疗药物。中医药治疗MDS已有多年历史。然而，其长期治疗效果和机制仍不清楚。在这项研究中，所有135例患者均接受了至少36个月的CM治疗。130例MDS-RCMD患者中，CM治疗后血液学改善的有效率为81.53%（106/130）; 5例MDS-RAEB患者中，CM治疗后骨髓CR的有效率为80%（4/5）。人类甲基化850 K微球芯片检测结果显示，5例MDS患者中有115个基因（50.88%）发生异常低甲基化，而3例正常人中有115个基因（50.88%）发生异常低甲基化。GO分析表明，这些低甲基化基因参与了许多与癌症相关的生物学功能和途径。CM治疗6个月后，5例MDS患者中有60个基因发生了高甲基化，DNMT 1蛋白表达水平显著升高。我们的研究表明，CM可以改善异常低甲基化通过增加DNMT 1的表达在MDS。这些数据支持含砷中药作为治疗MDS的一种创新的高甲基化诱导方案的临床应用。
Aberrant hypermethylation and hypomethylation both play important roles in myelodysplastic syndrome (MDS). Hypomethylating agents targeting hypermethylation have been employed for the MDS treatment, but the treatment effect is limited. Novel drugs for DNA hypomethylation-targeted therapy may be needed to improve clinic efficacy for the treatment of MDS. Chinese medicine (CM) herbs have been used to treat MDS for many years in our hospital. However, the long-term treatment effect and mechanism remain unclear. In this study, all 135 patients received CM treatment for at least 36 months. The response rates for CM treatment were 81.53% (106/130) for hematological improvement in 130 MDS-RCMD patients and 80% (4/5) for bone marrow CR in 5 MDS-RAEB patients, respectively. The Human Methylation 850K BeadChip showed that 115 genes (50.88%) were aberrantly hypomethylated in 5 MDS patients compared with 3 healthy individuals. GO-analysis showed that these hypomethylated genes participated in many cancer-related biological functions and pathways. Furthermore, 60 genes were hypermethylated and the protein expression level of DNMT1 was significantly increased in the 5 MDS patients after 6 months of CM treatment. Our study suggests that CM can improve aberrant hypomethylation by increasing DNMT1 expression in MDS. The data support the clinical application of CM herbs containing arsenic as an innovative hypermethylation-inducing regimen for the treatment of MDS.