hypermethylation is associated with mutation and indicates an adverse outcome in non-M3 acute myeloid leukemia.

OBJECTIVE

The purpose of this study was to evaluate the frequency of hypermethylation in patients with acute myeloid leukemia (AML), in an attempt to modify the current molecular model for disease prognosis.

MATERIALS AND METHODS

Aberrant 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, mRNA levels were detected by real-time quantitative polymerase chain reaction. Furthermore, hematological characteristics, cytogenetic abnormalities, and genetic aberrations were assessed. Finally, associations of hypermethylation with clinical outcomes were evaluated.

RESULTS

hypermethylation was observed in 23.0% of patients with non-M3 AML (52/226), but not in controls. Meanwhile, hypermethylation of the promoter was significantly associated with mutation. Furthermore, the log-rank test revealed that hypermethylation indicated decreased relapse-free survival (RFS) and overall survival (OS) in patients with non-M3 AML (=0.012 and =0.014, respectively). In multivariate analysis, hypermethylation was an independent prognostic factor for RFS (=0.040), but not for OS (=0.060).

CONCLUSION

Hypermethylation of the promoter is associated with mutation in non-M3 AML patients, likely indicating poor outcome. These findings provide a molecular basis for stratified diagnosis and prognostic evaluation.