title: Differentially expressed miRNAs in cytogenetic and molecular subtypes of pediatric acute myeloid leukemia.
abstract: BACKGROUND
  miRNAs regulate gene expression, and thus play an important role in critical cellular processes. Aberrant miRNA expression patterns have been found in various types of cancer. So far, information about the expression of miRNAs in pediatric acute myeloid leukemia is limited.
  
  
  METHODS
  We studied expression of miR-29a, -155, -196a, and -196b by stem-loop based RT-qPCR in 82 pediatric acute myeloid leukemia patients selected to represent relevant cytogenetic and molecular subgroups.
  
  
  RESULTS
  High miR-196a and -b expression was observed in patients carrying MLL gene rearrangements (P < 0.001), NPM1 mutations (P < 0.001), or FLT3-ITD in a cytogenetically normal background (P ≤ 0.02), compared to all other patients. In contrast, CEBPA mutated cases had a low expression of miR-196a and -b (P ≤ 0.001). Expression of miR-196a and -b was correlated with expression of neighboring HOXA and HOXB genes (Spearman's r = 0.46-0.82, P < 0.01). Expression of miR-155 was not related to cytogenetic features but high expression of miR-155 was observed in FLT3-ITD (P = 0.001) and NPM1-mutated cases (P = 0.04). Lower miR-29a expression was mainly observed in MLL-rearranged pediatric acute myeloid leukemia, specifically in cases carrying t(10;11) (P < 0.001).
  
  
  CONCLUSIONS
  We show aberrant expression of specific miRNAs in clinically relevant cytogenetic and molecular subgroups of pediatric acute myeloid leukemia, suggesting a role for these miRNAs in the underlying biology in these specific subgroups.
authors.affiliation: Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Astrid A
authors.initials: AA
authors.lastname: Danen-van Oorschot
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Kuipers
authors.forename: Susan
authors.initials: S
authors.lastname: Arentsen-Peters
authors.forename: Diana
authors.initials: D
authors.lastname: Schotte
authors.forename: Valerie
authors.initials: V
authors.lastname: de Haas
authors.forename: Jan
authors.initials: J
authors.lastname: Trka
authors.forename: André
authors.initials: A
authors.lastname: Baruchel
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: C Michel
authors.initials: CM
authors.lastname: Zwaan
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000032:analysis* / Q000502:physiology; D000090243:Nucleophosmin; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C491257:HOXB9 protein, human; D018398:Homeodomain Proteins; C524942:MIRN155 microRNA, human; C542543:MIRN196 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C000716967:NPM1 protein, human; C097899:homeobox protein HOXA9; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3