title: Differential expression of microRNAs in CD34+ cells of 5q- syndrome.
abstract: BACKGROUND
  Myelodysplastic syndrome with isolated chromosome 5q deletion (5q- syndrome) is a clonal stem cell disorder characterized by ineffective hematopoiesis. MicroRNAs (miRNAs) are important regulators of hematopoiesis and their aberrant expression was detected in some clonal hematopoietic disorders. We thus analyzed miRNA expressions in bone marrow CD34+ cells of 5q- syndrome patients. Further, we studied gene expressions of miR-143, miR-145, miR-378 and miR-146a mapped within the 5q deletion.
  
  
  RESULTS
  Using microarrays we identified 21 differently expressed miRNAs in 5q- patients compared to controls. Especially, miR-34a was markedly overexpressed in 5q- patients, suggesting its role in an increased apoptosis of bone marrow progenitors. Out of four miRNAs at del(5q), only miR-378 and miR-146a showed reduced gene expression in the patients. An integrative analysis of mRNA profiles and predicted putative targets defined potential downstream targets of the deregulated miRNAs. The list of targets included several genes that play an important role in the regulation of hematopoiesis (e.g. KLF4, LEF1, SPI1).
  
  
  CONCLUSIONS
  The study demonstrates global overexpression of miRNAs is associated with 5q- phenotype. Identification of hematopoiesis-relevant target genes indicates that the deregulated miRNAs may be involved in the pathogenesis of 5q- syndrome by a modulation of these targets. The expression data on miRNAs at del(5q) suggest the presence of mechanisms for compensation of a gene dosage.
authors.affiliation: Department of Molecular Genetics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic. Hana.Bruchova@uhkt.cz
authors.forename: Hana
authors.initials: H
authors.lastname: Votavova
authors.forename: Martina
authors.initials: M
authors.lastname: Grmanova
authors.forename: Michaela
authors.initials: M
authors.lastname: Dostalova Merkerova
authors.forename: Monika
authors.initials: M
authors.lastname: Belickova
authors.forename: Alzbeta
authors.initials: A
authors.lastname: Vasikova
authors.forename: Radana
authors.initials: R
authors.lastname: Neuwirtova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cermak
mesh_terms: D000748:Anemia, Macrocytic / Q000235:genetics / Q000378:metabolism; D018952:Antigens, CD34 / Q000096:biosynthesis* / Q000235:genetics; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D000090062:Kruppel-Like Factor 4; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D035683:MicroRNAs