title: Impact of Global and Gene-Specific DNA Methylation in de Novo or Relapsed Acute Myeloid Leukemia Patients Treated with Decitabine.
abstract: In this investigation, global DNA methylation patterns and the specific methylation status of 5 genes were studied in DNA from peripheral blood (PB) and impact on progression free survival (PFS) and overall-survival (OS) in patients with de novo or relapsed acute myeloid leukemia (AML) treated with decitabine-based regimens waas assessed. DNA was isolated from PB samples at the time of -1, 1, and 7 days of chemotherapy. Global methylation was determined by ELISA, and the CpG island DNA methylation profile of 5 genes using a DNA methylation PCR system. Our data demonstrated that patients with a high level of 5-mC had a poor prognosis after demethylation therapy and those who have low levels of 5-mC in PB achieved higher CR and better SO, but there was no significant correlation found between the 5-mC levels and other clinical features before treatment except the disease status. Higher methylation status of Sox2 and Oct4 genes was associated with differential response to demethylation therapy. A relatively low methylation percentage in one or both of these two genes was also associated with longer OS after decitabine based chemotherapy. We also suggest that global DNA and Oct-4/Sox2 methylation might impact on the pathogenesis of leukemia and play an important role in the initiation and progression. Moreover, dynamic analysis of 5-mC and Oct-4/Sox2 in peripheral blood nucleated cells of leukemia patients may provide clues to important molecular diagnostic and prognostic targets.
authors.affiliation: Department of Hematology, No.2 Affliliated Hospital, Soochow University, Suzhou, China E-mail : fjx3000@126.com.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Zhang
authors.forename: You-Qing
authors.initials: YQ
authors.lastname: Yuan
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Zhou
authors.forename: Zi-Yan
authors.initials: ZY
authors.lastname: Wang
authors.forename: Song-Guang
authors.initials: SG
authors.lastname: Ju
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Jin-Xiang
authors.initials: JX
authors.lastname: Fu
mesh_terms: D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018899:CpG Islands / Q000235:genetics; D004247:DNA / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D000077209:Decitabine; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D011379:Prognosis; D055748:SOXB1 Transcription Factors / Q000235:genetics; D055815:Young Adult
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D000077209:Decitabine; D004247:DNA; D001374:Azacitidine