Up-regulation of ABCB1/P-glycoprotein by escaping promoter hypermethylation indicates poor prognosis in hematologic malignancy patients with and without bone marrow transplantation

被引：11
|
作者：
Shi, Cheng-jun [1 ]
Wang, Fang [1 ]
Ren, Mei-feng [1 ]
Mi, Yan-jun [1 ]
Yan, Yan-yan [1 ]
To, Kenneth Kin Wah [3 ]
Dai, Chun-ling [1 ]
Wang, Yan-sheng [2 ]
Chen, Li-ming [1 ]
Tong, Xiu-zhen [2 ]
Liang, Yong-ju [1 ]
Fu, Li-wu [1 ]
机构：
[1] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol So China, Guangzhou 510060, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Hematol, Guangzhou 510060, Guangdong, Peoples R China
[3] Chinese Univ Hong Kong, Sch Pharm, Hong Kong, Hong Kong, Peoples R China
来源：
LEUKEMIA RESEARCH | 2011年 / 35卷 / 01期
关键词：
ATP binding cassette; Multidrug resistance; P-glycoprotein; Methylation; Hematologic malignancy; ACUTE MYELOID-LEUKEMIA; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; MDR1; GENE; EXPRESSION; CANCER; CELLS; METHYLATION; PROTEINS; OVEREXPRESSION;
D O I：
10.1016/j.leukres.2010.04.019
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
We investigated the correlation between MDR1 promoter methylation status and MDR1 expression in 228 hematologic malignancies patients and 90 healthy controls. High level of MDR1 mRNA correlated to promoter hypomethylation and strongly associated with poor prognosis indicated by 2-year survival rates, poor CR rate (without BMT) and high relapse rate (with BMT). Furthermore, relative luciferase activity of methylated MDR1 at promoter -50 region was significantly higher than that of the unmethylated. In addition, MDR1 in K562 cells elevated significantly after 5-Aza-dC treatment. In summary, MDR1 promoter hypomethylation conferred its up-regulation and indicated poor prognosis in patients with and without BMT. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码：73 / 79
页数：7
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