title: MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients.
abstract: Polycythemia vera (PV) and essential thrombocythemia (ET) are the two most common myeloproliferative neoplasms. The same JAK2(V617F) mutation can be found in both disorders and is able to recapitulate many of the phenotypic abnormalities of these diseases in the murine models. The disease phenotype is also influenced by other unknown genetic or epigenetic factors. MicroRNAs (miRNA) are 18-24 nucleotides single-stranded non-protein-coding RNAs that function primarily as gene repressors by binding to their target messenger RNAs. We performed miRNA expression profiling by oligonucleotide microarray analysis in purified peripheral blood CD34+ cells from eight JAK2(V617F)-positive PV patients and six healthy donors. A quantitative reverse-transcription polymerase chain reaction assay was used to verify differential miRNA expression. Since erythrocytosis is the only feature that distinguishes PV from ET, we also compared specific miRNA expression in the nucleated erythroid cells directly descended from the early erythroid progenitor cells of PV and ET patients. Our data indicate that significant miRNA deregulation occurs in PV CD34+ cells and confirm a genetic basis for the gender-specific differences that characterize PV with respect to miRNA. The results of our study also suggest that deregulated miRNAs may represent an important mechanism by which the PV erythrocytosis and ET thrombocytosis phenotypes are determined.
authors.affiliation: James J. Peters VA Medical Center, Bronx, NY 10468, USA. Huichun.Zhan@va.gov
authors.forename: Huichun
authors.initials: H
authors.lastname: Zhan
authors.forename: Christopher
authors.initials: C
authors.lastname: Cardozo
authors.forename: Wayne
authors.initials: W
authors.lastname: Yu
authors.forename: Antai
authors.initials: A
authors.lastname: Wang
authors.forename: Alison R
authors.initials: AR
authors.lastname: Moliterno
authors.forename: Chi V
authors.initials: CV
authors.lastname: Dang
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Spivak
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D016022:Case-Control Studies; D004920:Erythropoiesis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011087:Polycythemia Vera / Q000235:genetics*; D012737:Sex Factors; D013920:Thrombocythemia, Essential / Q000235:genetics*
chemical_list: D018952:Antigens, CD34; D035683:MicroRNAs