title: Up-regulation of ABCB1/P-glycoprotein by escaping promoter hypermethylation indicates poor prognosis in hematologic malignancy patients with and without bone marrow transplantation.
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.
authors.affiliation: State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Cheng-Jun
authors.initials: CJ
authors.lastname: Shi
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Mei-Feng
authors.initials: MF
authors.lastname: Ren
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Mi
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Yan
authors.forename: Kenneth Kin Wah
authors.initials: KK
authors.lastname: To
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Dai
authors.forename: Yan-Sheng
authors.initials: YS
authors.lastname: Wang
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Chen
authors.forename: Xiu-Zhen
authors.initials: XZ
authors.lastname: Tong
authors.forename: Yong-Ju
authors.initials: YJ
authors.lastname: Liang
authors.forename: Li-Wu
authors.initials: LW
authors.lastname: Fu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers