Prognostic significance of expression of a single microRNA, miR-181a, in cytogenetically normal acute myeloid leukemia: A cancer and leukemia group B study

Sebastian Schwind, Kati Maharry, Michael D. Radmacher, Krzysztof Mrózek, Kelsi B. Holland, Dean Margeson, Susan P. Whitman, Christopher Hickey, Heiko Becker, Klaus H. Metzeler, Peter Paschka, Claudia D. Baldus, Shujun Liu, Ramiro Garzon, Bayard L. Powell, Jonathan E. Kolitz, Andrew J. Carroll, Michael A. Caligiuri, Richard A. Larson, Guido MarcucciClara D. Bloomfield

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5257-5264
Number of pages8
JournalJournal of Clinical Oncology
Volume28
Issue number36
DOIs
StatePublished - Dec 20 2010
Externally publishedYes

Fingerprint Dive into the research topics of 'Prognostic significance of expression of a single microRNA, miR-181a, in cytogenetically normal acute myeloid leukemia: A cancer and leukemia group B study'. Together they form a unique fingerprint.

Cite this