TY - JOUR
T1 - Prognostic significance of expression of a single microRNA, miR-181a, in cytogenetically normal acute myeloid leukemia
T2 - A cancer and leukemia group B study
AU - Schwind, Sebastian
AU - Maharry, Kati
AU - Radmacher, Michael D.
AU - Mrózek, Krzysztof
AU - Holland, Kelsi B.
AU - Margeson, Dean
AU - Whitman, Susan P.
AU - Hickey, Christopher
AU - Becker, Heiko
AU - Metzeler, Klaus H.
AU - Paschka, Peter
AU - Baldus, Claudia D.
AU - Liu, Shujun
AU - Garzon, Ramiro
AU - Powell, Bayard L.
AU - Kolitz, Jonathan E.
AU - Carroll, Andrew J.
AU - Caligiuri, Michael A.
AU - Larson, Richard A.
AU - Marcucci, Guido
AU - Bloomfield, Clara D.
PY - 2010/12/20
Y1 - 2010/12/20
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2010.29.2953
DO - 10.1200/JCO.2010.29.2953
M3 - Article
C2 - 21079133
AN - SCOPUS:79251585678
SN - 0732-183X
VL - 28
SP - 5257
EP - 5264
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 36
ER -
