Objective: The purpose of this study was to evaluate the frequency of RASSF1A  hypermethylation in patients with acute myeloid leukemia (AML), in an attempt to modify the current molecular model for disease prognosis.
Materials and methods: Aberrant RASSF1A  promoter methylation levels were assessed in 226 newly diagnosed non-M3 AML patients and 30 apparently healthy controls, by quantitative methylation-specific polymerase chain reaction. Meanwhile, RASSF1A  mRNA levels were detected by real-time quantitative polymerase chain reaction. Furthermore, hematological characteristics, cytogenetic abnormalities, and genetic aberrations were assessed. Finally, associations of RASSF1A  hypermethylation with clinical outcomes were evaluated.
Results: RASSF1A  hypermethylation was observed in 23.0% of patients with non-M3 AML (52/226), but not in controls. Meanwhile, hypermethylation of the RASSF1A  promoter was significantly associated with ASXL1  mutation. Furthermore, the log-rank test revealed that RASSF1A  hypermethylation indicated decreased relapse-free survival (RFS) and overall survival (OS) in patients with non-M3 AML (P =0.012 and P =0.014, respectively). In multivariate analysis, RASSF1A  hypermethylation was an independent prognostic factor for RFS (P =0.040), but not for OS (P =0.060).
Conclusion: Hypermethylation of the RASSF1A  promoter is associated with ASXL1  mutation in non-M3 AML patients, likely indicating poor outcome. These findings provide a molecular basis for stratified diagnosis and prognostic evaluation.
Keywords: RASSF1A , hypermethylation, acute myeloid leukemia, clinical outcome, survival