title: Expression of a passenger miR-9* predicts favorable outcome in adults with acute myeloid leukemia less than 60 years of age.
abstract: In double-stranded miRNA/miRNA* duplexes, one of the strands represents an active miRNA, whereas another, known as a passenger strand (miRNA*), is typically degraded. MiR-9* is not detectable in normal myeloid cells. Here we show that miR-9* is expressed in 59% of acute myeloid leukemia (AML) cases and we investigate its clinical impact in 567 adults with de novo AML (age⩽60 years). AML cases with detectable miR-9* included a lower percentage of cases with favorable risk (P<0.001) as compared with those with no detectable miR-9*. High levels of miR-9* expression independently predicted for higher complete remission (odds ratio=1.28, P=0.013) and better event-free survival (EFS) (hazard ratio (HR)=0.86, P=0.001), relapse-free survival (RFS) (HR=0.84, P=0.008) and overall survival (OS) (HR=0.86, P=0.002). Among the subgroup of adverse risk patients, high miR-9* expressers had strikingly longer median survival than low miR-9* expressers (EFS: 16 vs 5 months, P=0.020; RFS: 12 vs 4, P=0.060; OS: 23 vs 8, P=0.021). Comparative transcriptome analysis suggests that miR-9* regulates genes involved in leukemogenesis, for example, MN1 and MLLT3. This is the first report showing that an miRNA* has prognostic value in AML.
authors.affiliation: Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Nowek
authors.affiliation: Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: S M
authors.initials: SM
authors.lastname: Sun
authors.affiliation: Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: M K
authors.initials: MK
authors.lastname: Dijkstra
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Bullinger
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Döhner
authors.affiliation: Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: S J
authors.initials: SJ
authors.lastname: Erkeland
authors.affiliation: Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Löwenberg
authors.affiliation: Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Jongen-Lavrencic
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged
chemical_list: C541874:MIRN92 microRNA, human; D035683:MicroRNAs