骨髓增生异常综合征P15^(INK4B)基因甲基化及药物去甲基化作用  

Methylation of P15^(INK4B) Gene in Patients with Myelodysplastic Syndromes and Demethylating Effects of Drugs

作　　者：叶雪石[1] 刘霆[1] 崔旭[1] 孟文彤[1] 席亚明[1] 

机构地区：[1]四川大学华西医院血液科,成都610041

出　　处：《四川大学学报（医学版）》2007年第1期57-59,共3页Journal of Sichuan University(Medical Sciences)

基　　金：美国纽约中华医学基金会科研基金(CMB00-722)资助

摘　　要：目的检测骨髓增生异常综合征(M DS)患者P 15INK 4B基因甲基化状况;探讨5-氮杂-2′-脱氧胞嘧啶(dec itab ine)和三氧化二砷(A s2O3)对M DS患者细胞的去甲基化作用。方法采用限制性内切酶联合PCR方法检测14例M DS患者P 15INK 4B基因甲基化,选择1例由M DS转化为急性白血病患者的外周血单个核细胞,分组分别加入dec itab ine和A s2O3进行处理,分析甲基化程度变化情况。结果低危组M DS患者(RCM D)均未发现P 15INK 4B基因甲基化,4例高危组M DS患者(RAEB)和4例M DS-AL患者发现P 15INK 4B基因甲基化。经dec itab ine和A s2O3处理后,M DS患者细胞的甲基化程度均降低50%左右。结论M DS的发生与P 15INK 4B基因甲基化密切相关,dec itab ine和A s2O3均对M DS患者细胞高度甲基化的P 15INK 4B基因具明显去甲基化作用。Objectives To detect the methylation of P15^INK4B gene in patients with myelodysplastie syndromes （MDS） and to investigate the demethylating effects of deeitabine and arsenic trioxide （As2O3）. Methods The bone marron mononuclear ceLLs from 14 MDS patients were coLLected. The methylation of P15^INK4B 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 P15^INK4B gene was detected in MDS patients with low risk of leukemia. The methylation of P15^INK4B 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 clown by 50%. Conclusion P15^INK4B gene hypermethylation is closely associated with MDS pathogenesis. Decitabine and As2O3 have demethylating effect on the cells from the MDS patient.

关 键 词：骨髓增生异常综合征 P15^INK4B基因甲基化 5-氮杂-2’-脱氧胞嘧啶 三氧化二砷 

分 类 号：R551.3[医药卫生—血液循环系统疾病]