title: Genome-wide miRNA profiling in myelodysplastic syndrome with del(5q) treated with lenalidomide.
abstract: OBJECTIVE
  Lenalidomide is a potent drug with pleiotropic effects in patients with myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 5 [del(5q)]. We investigated its effect on regulation of microRNA (miRNA) expression profiles in del(5q) patients with MDS in vivo.
  
  
  METHODS
  We used miRNA expression microarrays to study changes in miRNA levels in peripheral blood CD14+ monocytes collected from patients before and during lenalidomide treatment and compared them with those from healthy donors.
  
  
  RESULTS
  Before treatment, we observed strong upregulation of pro-apoptotic miR-34a and miR-34a* that diminished during lenalidomide exposure. Upregulation of HOX-related miR-196b and erythroid-specific miR-451 seen in untreated patients remained unchanged after the treatment. At the time of hematologic response, expression of several miRNAs clustering to the 14q32 locus was reduced. Additionally, we focused more deeply on miRNAs from the 5q commonly deleted region and found that levels of miR-378 and miR-378* followed haploinsufficiency trend.
  
  
  CONCLUSIONS
  This report describes changes in miRNA expression in del(5q) patients with MDS treated with lenalidomide, likely arising from deregulation of pathways implicated in lenalidomide action.
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Michaela Dostalova
authors.initials: MD
authors.lastname: Merkerova
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Krejcik
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Belickova
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hrustincova
authors.affiliation: Department of Cybernetics, Faculty of Electrical Engineering, Czech Technical University, Prague, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Klema
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Eliška
authors.initials: E
authors.lastname: Stara
authors.affiliation: Center of Oncocytogenetics, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Zemanova
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.|Center of Oncocytogenetics, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Kyra
authors.initials: K
authors.lastname: Michalova
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cermak
authors.affiliation: First Department of Medicine, General University Hospital, Prague, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Jonasova
mesh_terms: D000368:Aged; D000748:Anemia, Macrocytic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002872:Chromosome Deletion; D002883:Chromosomes, Human, Pair 14; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D057895:Haploinsufficiency; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000077269:Lenalidomide; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D012326:RNA Splicing; D015398:Signal Transduction; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D007155:Immunologic Factors; C542543:MIRN196 microRNA, human; C522425:MIRN34 microRNA, human; C526012:MIRN378 microRNA, human; C531201:MIRN451 microRNA, human; D035683:MicroRNAs; D013792:Thalidomide; D000077269:Lenalidomide
keywords: del(5q); lenalidomide; miRNA; myelodysplastic syndromes