Up-regulation of ABCB1/P-glycoprotein by escaping promoter hypermethylation indicates poor prognosis in hematologic malignancy patients with and without bone marrow transplantation
Cheng-jun Shi, Fang Wang, Mei-feng Ren, Yan-jun Mi, Yan-yan Yan, Kenneth Kin Wah To, Chun-ling Dai, Yan-sheng Wang, Li-ming Chen, Xiu-zhen Tong, Yong-ju Liang, Li-wu Fu
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.