1. Up-regulation of ABCB1/P-glycoprotein by escaping promoter hypermethylation indicates poor prognosis in hematologic malignancy patients with and without bone marrow transplantation
- Author
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Yan sheng Wang, Cheng Jun Shi, Mei feng Ren, Yan Yan Yan, Yan Jun Mi, Chun Ling Dai, Fang Wang, Yong Ju Liang, Li Ming Chen, Xiu Zhen Tong, Kenneth K.W. To, and Li Wu Fu
- Subjects
Adult ,Male ,Cancer Research ,ATP Binding Cassette Transporter, Subfamily B ,Adolescent ,physiological processes ,Flow cytometry ,Young Adult ,Downregulation and upregulation ,polycyclic compounds ,medicine ,Humans ,Luciferase ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Young adult ,Child ,Promoter Regions, Genetic ,neoplasms ,Bone Marrow Transplantation ,DNA Primers ,P-glycoprotein ,Base Sequence ,biology ,medicine.diagnostic_test ,Reverse Transcriptase Polymerase Chain Reaction ,Hematology ,Methylation ,DNA Methylation ,Middle Aged ,Flow Cytometry ,Prognosis ,Up-Regulation ,Oncology ,Child, Preschool ,Hematologic Neoplasms ,DNA methylation ,Cancer research ,biology.protein ,Female ,K562 cells - Abstract
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.
- Published
- 2011
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