The prognostic relevance of miR-212 expression with survival in cytogenetically and molecularly heterogeneous AML

Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous disease, characterized by various cytogenetic and molecular abnormalities, many of which may express prognostic value. MicroRNAs (miRNAs) are a class of small regulatory RNAs. The prognostic value of miRNAs in AML is yet to be determined. Here, we set out to identify miRNAs that are consistent significant prognostic determinants, independent from other known prognostic factors. A discovery cohort (n=167) and validation cohort (n=409) of a heterogeneous AML population were used to reliably identify miRNAs with prognostic value. We report miR-212 as an independent prognostic factor, significantly associated with a prolonged overall survival (OS) and also event-free and relapse-free survival in a discovery cohort (hazard ratio (HR)s=0.77, P=0.015 for OS) that was subsequently confirmed in an independent validation cohort of 409 cases (HR=0.83, P=0.016). The prognostic significance and the prevalence of high miR-212 did not correlate with specific (cyto)genetic subtypes of AML. High miR-212 expression levels are associated with a gene expression profile that is significantly enriched for genes involved in the immune response. MiR-212 may improve the current prognostic risk stratification of mixed AML including normal karyotype AML and AML with cytogenetic and molecular abnormalities.