title: MicroRNA expression in cytogenetically normal acute myeloid leukemia.
abstract: BACKGROUND
  A role of microRNAs in cancer has recently been recognized. However, little is known about the role of microRNAs in acute myeloid leukemia (AML).
  
  
  METHODS
  Using microRNA expression profiling, we studied samples of leukemia cells from adults under the age of 60 years who had cytogenetically normal AML and high-risk molecular features--that is, an internal tandem duplication in the fms-related tyrosine kinase 3 gene (FLT3-ITD), a wild-type nucleophosmin (NPM1), or both. A microRNA signature that was associated with event-free survival was derived from a training group of 64 patients and tested in a validation group of 55 patients. For the latter, a microRNA compound covariate predictor (called a microRNA summary value) was computed on the basis of weighted levels of the microRNAs forming the outcome signature.
  
  
  RESULTS
  Of 305 microRNA probes, 12 (including 5 representing microRNA-181 family members) were associated with event-free survival in the training group (P<0.005). In the validation group, the microRNA summary value was inversely associated with event-free survival (P=0.03). In multivariable analysis, the microRNA summary value remained associated with event-free survival (P=0.04) after adjustment for the allelic ratio of FLT3-ITD to wild-type FLT3 and for the white-cell count. Using results of gene-expression microarray analysis, we found that expression levels of the microRNA-181 family were inversely correlated with expression levels of predicted target genes encoding proteins involved in pathways of innate immunity mediated by toll-like receptors and interleukin-1beta.
  
  
  CONCLUSIONS
  A microRNA signature in molecularly defined, high-risk, cytogenetically normal AML is associated with the clinical outcome and with target genes encoding proteins involved in specific innate-immunity pathways.
authors.affiliation: Division of Hematology and Oncology, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA. guido.marcucci@osumc.edu
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Michael D
authors.initials: MD
authors.lastname: Radmacher
authors.forename: Kati
authors.initials: K
authors.lastname: Maharry
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.forename: Amy S
authors.initials: AS
authors.lastname: Ruppert
authors.forename: Peter
authors.initials: P
authors.lastname: Paschka
authors.forename: Tamara
authors.initials: T
authors.lastname: Vukosavljevic
authors.forename: Susan P
authors.initials: SP
authors.lastname: Whitman
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Baldus
authors.forename: Christian
authors.initials: C
authors.lastname: Langer
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Ramiro
authors.initials: R
authors.lastname: Garzon
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D015347:RNA Probes; D012334:RNA, Neoplasm / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000071230:Transcriptional Regulator ERG; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C072312:ERG protein, human; D005819:Genetic Markers; D035683:MicroRNAs; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D015347:RNA Probes; D012334:RNA, Neoplasm; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3