Prognostic significance of expression of a single microRNA, miR-181a, in cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study

J Clin Oncol. 2010 Dec 20;28(36):5257-64. doi: 10.1200/JCO.2010.29.2953. Epub 2010 Nov 15.

Abstract

Purpose: To evaluate the prognostic significance of expression levels of a single microRNA, miR-181a, in the context of established molecular markers in cytogenetically normal acute myeloid leukemia (CN-AML), and to gain insight into the leukemogenic role of miR-181a.

Patients and methods: miR-181a expression was measured in pretreatment marrow using Ohio State University Comprehensive Cancer Center version 3.0 arrays in 187 younger (<60 years) adults with CN-AML. Presence of other molecular prognosticators was assessed centrally. A gene-expression profile associated with miR-181a expression was derived using microarrays and evaluated by Gene-Ontology analysis.

Results: Higher miR-181a expression associated with a higher complete remission (CR) rate (P=.04), longer overall survival (OS; P=.01) and a trend for longer disease-free survival (DFS; P=.09). The impact of miR-181a was most striking in poor molecular risk patients with FLT3-internal tandem duplication (FLT3-ITD) and/or NPM1 wild-type, where higher miR-181a expression associated with a higher CR rate (P=.009), and longer DFS (P<.001) and OS (P<.001). In multivariable analyses, higher miR-181a expression was significantly associated with better outcome, both in the whole patient cohort and in patients with FLT3-ITD and/or NPM1 wild-type. These results were also validated in an independent set of older (≥60 years) patients with CN-AML. A miR-181a-associated gene-expression profile was characterized by enrichment of genes usually involved in innate immunity.

Conclusion: To our knowledge, we provide the first evidence that the expression of a single microRNA, miR-181a, is associated with clinical outcome of patients with CN-AML and may refine their molecular risk classification. Targeted treatments that increase endogenous levels of miR-181a might represent novel therapeutic strategies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Gene Expression Profiling
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • MicroRNAs / genetics*
  • Middle Aged
  • Nucleophosmin
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Young Adult

Substances

  • MIrn181 microRNA, human
  • MicroRNAs
  • NPM1 protein, human
  • Nucleophosmin