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.
Highlights
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults
A decrease of global methylation status was observed in all the patients treated with decitabine based chemotherapy at day1 or days 7, but it seemed that the 5-mC levels decreased significantly at day 7 in the de novo acute myeloid leukemia (AML) and relapsed/refractory AML
We found that a relatively high DNA global methylation was an independent prognostic factor in patients AML before treatment and those whose methylation status decreased after demethylation therapy seemed to have higher CR rate and longer progression free survival (PFS)
Summary
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. It is characterized by an uncontrolled proliferation and differentiation block in immature hematopoietic stem cells and progenitor cells (HSPCs) resulting in an accumulation of immature blasts (Claus et al, 2010). Extraordinary progresses in diagnosis and therapy, the outcome of AML patients remains poor, especially in elderly. Less than 50% of adult AML patients have a 5-year overall survival (OS) whilst about 20% of elderly survives more than 2 years and the treatment remains a challenge (Dohner et al, 2010; Grossmann et al, 2012; Patel et al., 2012; Kadia et al 2015).
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