Up-regulation of ABCB1/P-glycoprotein by escaping promoter hypermethylation indicates poor prognosis in hematologic malignancy patients with and without bone marrow transplantation.
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.
Shi
Cheng-Jun
CJ
State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
Wang
Fang
F
Ren
Mei-Feng
MF
Mi
Yan-Jun
YJ
Yan
Yan-Yan
YY
To
Kenneth Kin Wah
KK
Dai
Chun-Ling
CL
Wang
Yan-Sheng
YS
Chen
Li-Ming
LM
Tong
Xiu-Zhen
XZ
Liang
Yong-Ju
YJ
Fu
Li-Wu
LW
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
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers