title: MicroRNAs distinguish cytogenetic subgroups in pediatric AML and contribute to complex regulatory networks in AML-relevant pathways.
abstract: BACKGROUND
  The role of microRNAs (miRNAs), important post-transcriptional regulators, in the pathogenesis of acute myeloid leukemia (AML) is just emerging and has been mainly studied in adults. First studies in children investigate single selected miRNAs, however, a comprehensive overview of miRNA expression and function in children and young adults is missing so far.
  
  
  RESULTS
  We here globally identified differentially expressed miRNAs between AML subtypes in a survey of 102 children and adolescent. Pediatric samples with core-binding factor AML and promyelocytic leukemia could be distinguished from each other and from MLL-rearranged AML subtypes by differentially expressed miRNAs including miR-126, -146a, -181a/b, -100, and miR-125b. Subsequently, we established a newly devised immunoprecipitation assay followed by rapid microarray detection for the isolation of Argonaute proteins, the hallmark of miRNA targeting complexes, from cell line models resembling core-binding factor and promyelocytic leukemia. Applying this method, we were able to identify Ago-associated miRNAs and their targeted mRNAs.
  
  
  CONCLUSIONS
  miRNAs as well as their mRNA-targets showed binding preferences for the different Argonaute proteins in a cell context-dependent manner. Bioinformatically-derived pathway analysis suggested a concerted action of all four Argonaute complexes in the regulation of AML-relevant pathways. For the first time, to our knowledge, a complete AML data set resulting from carefully devised biochemical isolation experiments and analysis of Ago-associated miRNAs and their target-mRNAs is now available.
authors: Heinrich-Heine University Düsseldorf, Medical Faculty, Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Düsseldorf, Germany.
authors: Svenja
authors: S
authors: Daschkey
authors: Silja
authors: S
authors: Röttgers
authors: Anamika
authors: A
authors: Giri
authors: Jutta
authors: J
authors: Bradtke
authors: Andrea
authors: A
authors: Teigler-Schlegel
authors: Gunter
authors: G
authors: Meister
authors: Arndt
authors: A
authors: Borkhardt
authors: Pablo
authors: P
authors: Landgraf
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D060565:Argonaute Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D003582:Cytogenetics; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000145:classification / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
chemical_list: D060565:Argonaute Proteins; C544266:MIRN100 microRNA, human; C531888:MIRN125 microRNA, human; C527111:MIRN126 microRNA, human; C542542:MIRN146 microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D020033:Protein Isoforms