Overexpressed let-7a-3 is associated with poor outcome in acute myeloid leukemia

Abstract

Dysregulation of microRNA let-7a-3 has been identified in several solid tumors and is associated with prognosis of patients. However, the pattern of let-7a-3 expression and the impact on prognosis has not yet been studied in acute myeloid leukemia (AML). The purpose of this study is to investigate the expression status of let-7a-3 and its clinical significance in AML patients using real-time quantitative PCR. Overexpression of let-7a-3 was identified in 25 of 102 (25%) de novo AML. There was no significant difference in age, blood parameters, FAB/WHO subtypes, karyotype risks and nine gene mutations (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, C/EBPA and N/K-RAS) between patients with and without let-7a-3 overexpression (P>0.05). The patients with let-7a-3 overexpression had similar rates of complete remission (CR) as those without let-7a-3 overexpression (50% vs. 56%, P=0.693). Although the overall survival (OS) of AML patients with let-7a-3 overexpression (median 12 months,) was shorter than those without overexpression (median 25 months), the difference was not statistically significant (P=0.228). However, among those 51 obtained CR, patients with let-7a-3 overexpression had significantly shorter OS than those without let-7a-3 overexpression (P=0.029). The difference in relapse-free survival (RFS) was also significant between two groups (P=0.005). These findings suggest that let-7a-3 overexpression is a common event and is associated with poor clinical outcome in AML.

Keywords: Acute myeloid leukemia; MicroRNA; Prognosis; let-7a-3.