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[骨髓增生异常综合征患者P15INK4B基因甲基化及药物去甲基化作用]

[Methylation of P15INK4B gene in patients with myelodysplastic syndromes and demethylating effects of drugs].

作者信息

Ye Xue-shi, Liu Ting, Cui Xu, Meng Wen-tong, Xi Ya-ming

机构信息

Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2007 Jan;38(1):57-9.

PMID:17294728
Abstract

OBJECTIVES

To detect the methylation of P15INK4B gene in patients with myelodysplastic syndromes (MDS) and to investigate the demethylating effects of decitabine and arsenic trioxide (As2O3).

METHODS

The bone marron mononuclear cells from 14 MDS patients were collected. The methylation of P15INK4B gene was detected with restrictive endonucleases combined with PCR technique. The peripheral blood mononuclear cells from one of the patients who had progressed into acute leukemia were treated with decitabine and As2O3 in vitro to test the change of methylation.

RESULTS

No methylation of P15INK4B gene was detected in MDS patients with low risk of leukemia. The methylation of P15K4B gene was found in 4 MDS patients with high-risk of leukemia and 4 patients who had progressed from MDS to acute leukemia. After exposed to decitabine or As2O3, the methylation went down by 50%.

CONCLUSION

P15INK4B gene hypermethylation is closely associated with MDS pathogenesis. Decitabine and As2O3 have demethylating effect on the cells from the MDS patient.

摘要

目的

检测骨髓增生异常综合征(MDS)患者P15INK4B基因的甲基化情况,并研究地西他滨和三氧化二砷(As2O3)的去甲基化作用。

方法

收集14例MDS患者的骨髓单个核细胞。采用限制性内切酶联合PCR技术检测P15INK4B基因的甲基化情况。对1例已进展为急性白血病的患者的外周血单个核细胞进行体外地西他滨和As2O3处理,检测甲基化变化。

结果

白血病低危的MDS患者未检测到P15INK4B基因甲基化。4例白血病高危的MDS患者及4例从MDS进展为急性白血病的患者中发现P15K4B基因甲基化。经地西他滨或As2O3处理后,甲基化水平下降50%。

结论

P15INK4B基因高甲基化与MDS发病机制密切相关。地西他滨和As2O3对MDS患者细胞有去甲基化作用。

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Sichuan Da Xue Xue Bao Yi Xue Ban. 2007 Jan;38(1):57-9.
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