CEBPA methylation as a prognostic biomarker in patients with de novo acute myeloid leukemia

Hypermethylation of the distal CEBPA promoter region has been reported to result in the downregulation of CEBPA expression in several malignancies. However, the clinical implication of CEBPA hypermethylation in acute myeloid leukemia (AML) remains unclear. To investigate the correlation between CEBPA hypermethylation and clinical features in AML, quantitative MassARRAY analyses for CEBPA methylation status were performed on a cohort of 193 patients. High CEBPA methylation group (CEBPAhigh-meth, n28) and low methylation group (CEBPA low-meth, n165) were defined by using two-way hierarchical clustering. With a median follow-up of 48 months, among the 125 patients receiving standard induction therapy, CEBPAhigh-meth was associated with better treatment response (complete remission rate 93.3% versus 73.6%, P0.116). In patients with normal karyotype and without CEBPA and NPM1 mutations, the CEBPAhigh-meth had longer overall survival (OS) than the CEBPA low-meth (P0.028). Multivariate analysis further supported that the CEBPA methylation was an independent prognostic factor for disease free-survival (hazard ratio0.416; 95% confidence interval, 0.223-0.777, P0.006) and OS (hazard ratio0.406; 95% confidence interval, 0.166-0.996, P0.050). We conclude that CEBPA methylation status is a useful prognostic biomarker for AML patients. ? 2011 Macmillan Publishers Limited All rights reserved.