title: Prognostic significance of expression of a single microRNA, miR-181a, in cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Ohio State University, Comprehensive Cancer Center, Biomedical Research Tower, 460 W 12th Ave, Columbus, OH 43210, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schwind
authors.forename: Kati
authors.initials: K
authors.lastname: Maharry
authors.forename: Michael D
authors.initials: MD
authors.lastname: Radmacher
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.forename: Kelsi B
authors.initials: KB
authors.lastname: Holland
authors.forename: Dean
authors.initials: D
authors.lastname: Margeson
authors.forename: Susan P
authors.initials: SP
authors.lastname: Whitman
authors.forename: Christopher
authors.initials: C
authors.lastname: Hickey
authors.forename: Heiko
authors.initials: H
authors.lastname: Becker
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Metzeler
authors.forename: Peter
authors.initials: P
authors.lastname: Paschka
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Baldus
authors.forename: Shujun
authors.initials: S
authors.lastname: Liu
authors.forename: Ramiro
authors.initials: R
authors.lastname: Garzon
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000293:Adolescent; D000328:Adult; D020869:Gene Expression Profiling; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D000090243:Nucleophosmin; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D055815:Young Adult
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C000716967:NPM1 protein, human; D000090243:Nucleophosmin