Expression of a passenger miR-9∗ predicts favorable outcome in adults with acute myeloid leukemia less than 60 years of age

Abstract

In double-stranded miRNA/miRNA∗ duplexes, one of the strands represents an active miRNA, whereas another, known as a passenger strand (miRNA∗), is typically degraded. MiR-9∗ is not detectable in normal myeloid cells. Here we show that miR-9∗ is expressed in 59% of acute myeloid leukemia (AML) cases and we investigate its clinical impact in 567 adults with de novo AML (age≤60 years). AML cases with detectable miR-9∗ included a lower percentage of cases with favorable risk (P<0.001) as compared with those with no detectable miR-9∗. High levels of miR-9∗ expression independently predicted for higher complete remission (odds ratio=1.28, P=0.013) and better event-free survival (EFS) (hazard ratio (HR)=0.86, P=0.001), relapse-free survival (RFS) (HR=0.84, P=0.008) and overall survival (OS) (HR=0.86, P=0.002). Among the subgroup of adverse risk patients, high miR-9∗ expressers had strikingly longer median survival than low miR-9∗ expressers (EFS: 16 vs 5 months, P=0.020; RFS: 12 vs 4, P=0.060; OS: 23 vs 8, P=0.021). Comparative transcriptome analysis suggests that miR-9∗ regulates genes involved in leukemogenesis, for example, MN1 and MLLT3. This is the first report showing that an miRNA∗ has prognostic value in AML.