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清黄散()联合补肺益肾汤()通过调控 DNA 甲基化治疗难治性多系发育异常细胞减少症患者的疗效。

Effect of Qinghuang Powder () Combined with Bupi Yishen Decoction () in Treating Patients with Refractory Cytopenia with Multilineage Dysplasia through Regulating DNA Methylation.

机构信息

National Hematological Medical Center of Traditional Chinese Medicine, Department of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.

出版信息

Chin J Integr Med. 2019 May;25(5):354-359. doi: 10.1007/s11655-018-2554-9. Epub 2018 Mar 2.

DOI:10.1007/s11655-018-2554-9
PMID:29500545
Abstract

OBJECTIVE

To explore the effect of Qinghuang Powder (QHP,()combined with Bupi Yishen Decoction (BPYS, ) on myelodysplastic syndromes (MDS) patients with refractory cytopenia with multilineage dysplasia (RCMD) and determine the change of DNA methylation in MDS-RCMD patients after the treatment of Chinese medicine formula.

METHODS

All 308 MDS-RCMD patients were treated with QHP combined with BPYS for 2 months at least, absolute neutrophil count (ANC), hemoglobin (Hb), platelets (PLT), primitive bone marrow cells and chromosome karyotype were chosen as the main evaluation indexes to analyze the treatment effect according to criteria from the MDS International Working Group. Then 43 bone marrow samples from 15 MDS-RCMD patients and 28 healthy donors were obtained for the examination of DNA methylation. Gene Ontology (GO) and Pathway analysis were applied to analyze the methylation data.

RESULTS

The overall MDS response rate to QHP was 61.68% (190/360) including hematologic improvement-neutrophil (HI-N) or hematologic improvement-erythroid (HI-E) or hematologic improvement-platelet (HI-P). Patients with anemia had a better response rate than patients with neutropenia or thrombocypenia (55.88% vs 31.54% or 55.88% vs. 36.9%). The DNA methylation microarray analysis disclosed that 4,257 hypermethylated genes were demethylated upon the treatment with QHP and BPYS. GO analysis and Pathway analysis showed that these demethylated genes were involved in a lot of tumor-related pathways and functions.

CONCLUSIONS

QHP combined with BPYS could effectively treat MDS-RCMD patients through hematologic improvement (HI-N, HI-P or HI-E) and PLT and RBC transfusion independence due to the demethylation, thereby providing another choice for the treatment of patients with MDS-RCMD.

摘要

目的

探讨青黄散(QHP)联合补髓益血汤(BPYS)治疗骨髓增生异常综合征伴难治性血细胞减少伴多系发育异常(RCMD)的疗效,并确定中药方剂治疗后骨髓增生异常综合征-RCMD 患者 DNA 甲基化的变化。

方法

所有 308 例 MDS-RCMD 患者均采用 QHP 联合 BPYS 治疗至少 2 个月,根据 MDS 国际工作组的标准,选择绝对中性粒细胞计数(ANC)、血红蛋白(Hb)、血小板(PLT)、原始骨髓细胞和染色体核型作为主要评价指标,分析治疗效果。然后从 15 例 MDS-RCMD 患者和 28 例健康供者中获得 43 例骨髓样本,进行 DNA 甲基化检测。应用基因本体论(GO)和通路分析对甲基化数据进行分析。

结果

QHP 总反应率为 61.68%(190/360),包括血液学改善-中性粒细胞(HI-N)或血液学改善-红细胞(HI-E)或血液学改善-血小板(HI-P)。贫血患者的反应率优于中性粒细胞减少或血小板减少患者(55.88%比 31.54%或 55.88%比 36.9%)。DNA 甲基化微阵列分析显示,4257 个高甲基化基因经 QHP 和 BPYS 治疗后去甲基化。GO 分析和通路分析表明,这些去甲基化基因参与了许多肿瘤相关通路和功能。

结论

QHP 联合 BPYS 通过血液学改善(HI-N、HI-P 或 HI-E)和血小板及红细胞输注独立性治疗 MDS-RCMD 患者,可有效降低骨髓增生异常综合征-RCMD 患者的 DNA 甲基化水平,为治疗骨髓增生异常综合征-RCMD 患者提供了另一种选择。

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