Prognostic Significance of Expression of a Single MicroRNA, miR-181a, in Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study
| Autor: | Kati Maharry, Michael D. Radmacher, Claudia D. Baldus, Kelsi B. Holland, Krzysztof Mrózek, Klaus H. Metzeler, Richard A. Larson, Heiko Becker, Peter Paschka, Andrew J. Carroll, Sebastian Schwind, Dean Margeson, Christopher Hickey, Bayard L. Powell, Susan P. Whitman, Clara D. Bloomfield, Jonathan E. Kolitz, Michael A. Caligiuri, Ramiro Garzon, Guido Marcucci, Shujun Liu |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Oncology Cancer Research medicine.medical_specialty NPM1 Myeloid Adolescent Context (language use) Leukemogenic Young Adult Internal medicine Original Reports microRNA medicine Humans Oligonucleotide Array Sequence Analysis business.industry Gene Expression Profiling Cancer Middle Aged Prognosis medicine.disease Gene expression profiling Leukemia Myeloid Acute MicroRNAs Leukemia medicine.anatomical_structure Immunology business Nucleophosmin |
| Zdroj: | Journal of Clinical Oncology. 28:5257-5264 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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