Impact of Global and Gene-Specific DNA Methylation in de Novo or Relapsed Acute Myeloid Leukemia Patients Treated with Decitabine

Zhang, Li-Ying; Yuan, You-Qing; Zhou, Dong-Ming; Wang, Zi-Yan; Ju, Song-Guang; Sun, Yu; Li, Jun; Fu, Jin-Xiang

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자료유형: 학술저널

저자정보: Zhang, Li-Ying (Department of Hematology, No.2 Affiliated Hospital, Soochow University) Yuan, You-Qing (Department of Hematology, No.2 Affiliated Hospital, Soochow University) Zhou, Dong-Ming (Department of Hematology, No.2 Affiliated Hospital, Soochow University) Wang, Zi-Yan (Department of Hematology, No.2 Affiliated Hospital, Soochow University) Ju, Song-Guang (Department of Immunology, Medical College of Soochow University) Sun, Yu (Department of Hematology, No.2 Affiliated Hospital, Soochow University) Li, Jun (Department of Hematology, No.2 Affiliated Hospital, Soochow University) Fu, Jin-Xiang (Department of Hematology, No.2 Affiliated Hospital, Soochow University)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제17권 제1호

발행연도: 2016.1

수록면: 431 - 437 (7page)

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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.

#Acute myeloid leukemia #global DNA methylation #5-methylcytosine #Sox2 #Oct4

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