CTNNA1 hypermethylation, a frequent event in acute myeloid leukemia, is independently associated with an adverse outcome

Abstract

The aim of this study is to evaluate the frequency of CTNNA1 hypermethylation in acute myeloid leukemia (AML) patients in an attempt to improve molecular prognostic model. CTNNA1 promoter methylation levels in 319 newly diagnosed AML patients were detected using quantitative methylation-specific polymerase chain reaction (qMS-PCR). Furthermore, hematological characteristics, cytogenetic abnormalities, and genetic mutation status were analyzed, followed by assessment of clinical impact. Our findings demonstrated that CTNNA1 hypermethylation was observed in 25% AML patients. Hypermethylation of the CTNNA1 promoter was associated with unfavorable karyotype, and also possessed the higher frequency of coexisting with ASXL1 and RUNX1 mutations. Patients with CTNNA1 hypermethylation exhibited the shorter relapse-free survival (RFS) and overall survival (OS) in the whole AML and non-M3 AML patients. Moreover, patients with the higher methylation levels had more aggressive course than those with relative lower levels. In multivariate analyses, CTNNA1 hypermethylation was an independent factor predicting for poor RFS, but not for OS. In conclusion, CTNNA1 hypermethylation may be a reliable factor for improving prognostic molecular model for AML.