title: MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia.
abstract: Acute myeloid leukemia (AML) is a highly diverse disease characterized by various cytogenetic and molecular abnormalities. MicroRNAs are small noncoding RNAs that show variable expression during myeloid differentiation. MicroRNA expression in marrow blasts in 215 cases of newly diagnosed and (cyto)genetically defined AML was assessed using quantitative reverse-transcription-polymerase chain reaction (RT-PCR) for 260 human microRNAs. In the same series, mRNA gene expression profiles were established, allowing a direct comparison between microRNA and mRNA expression. We show that microRNA expression profiling following unsupervised analysis reveals distinctive microRNA signatures that correlate with cytogenetic and molecular subtypes of AML (ie, AMLs with t(8;21), t(15;17), inv(16), NPM1, and CEBPA mutations). Significantly differentially expressed microRNAs for genetic subtypes of AML were identified. Specific microRNAs with established oncogenic and tumor suppressor functions, such as microRNA-155, microRNA-21, and let-7, appear to be associated with particular subtypes. Combinations of selected sets of microRNAs could predict cytogenetically normal AML with mutations in the genes of NPM1 and CEBPA and FLT3-ITD with similar accuracy as mRNA probe set combinations defined by gene expression profiling. MicroRNA expression apparently bears specific relationships to the heterogeneous pathobiology of AML. Distinctive microRNA signatures appear of potential value in the clinical diagnosis of AML.
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands. m.lavrencic@erasmusmc.nl
authors.forename: Mojca
authors.initials: M
authors.lastname: Jongen-Lavrencic
authors.forename: Su Ming
authors.initials: SM
authors.lastname: Sun
authors.forename: Menno K
authors.initials: MK
authors.lastname: Dijkstra
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Valk
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
mesh_terms: D001752:Blast Crisis / Q000473:pathology; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015973:Gene Expression Regulation, Leukemic; D018740:Genetic Heterogeneity; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D050505:Mutant Proteins; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D035683:MicroRNAs; D050505:Mutant Proteins; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3