Clinical characteristics and prognosis of acute myeloid leukemia associated with DNA-methylation regulatory gene mutations
2016
In recent years, it has been reported that DNA-methylation regulatory gene mutation - mutation of the genes that regulate gene expression through DNA methylation - is observed with high frequency in acute myeloid leukemia. The objective of the present study was to elucidate the clinical characteristics and prognosis of acute myeloid leukemia with associated DNA-methylation regulatory gene mutation. The subjects were 308 patients with acute myeloid leukemia. DNA-methylation regulatory gene mutation was observed in 135 of the 308 cases (43.8%). acute myeloid leukemia associated with DNA-methylation regulatory gene mutation was more frequent in older patients ( p <0.0001), and in patients with intermediate cytogenetic risk ( p <0.0001) accompanied by high white blood cell count ( p =0.0032). DNA-methylation regulatory gene mutation was an unfavorable prognostic factor for overall survival in cases overall ( p =0.0018) and in patients aged ≤ 70 years, in patients with intermediate cytogenetic risk, and in FLT3 -ITD-negative patients ( p =0.0409). Of patients with DNA-methylation regulatory gene mutation, 26.7% were found to have two or more DNA-methylation regulatory gene mutations. In patients with DNA-methylation regulatory gene mutation, prognosis worsened with increasing number of mutations. In multivariate analysis also, DNA-methylation regulatory gene mutation was an independent unfavorable prognostic factor for overall survival ( p =0.0424). Moreover, cases with DNA-methylation regulatory gene mutation that received allogeneic stem cell transplantation in the first remission period had a significantly more favorable prognosis than those that did not receive allogeneic stem cell transplantation ( p =0.0254). Our study establishes that DNA-methylation regulatory gene mutation is an important unfavorable prognostic factor in acute myeloid leukemia.
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