title: Role of JAK2 V617F mutation and aberrant expression of microRNA-143 in myeloproliferative neoplasms.
abstract: BACKGROUND
  Myeloproliferative neoplasms (MPNs) are clonal myeloid disorders characterized by the overproduction of mature blood cells. The pathogenetic hallmark of MPNs is the dysregulation of JAK-STAT signaling, usually associated with the JAK2 V617F mutation. Multiple additional genetic and epigenetic alterations that constitutively activate the JAK-STAT signaling pathway have been described, including the modulation of the microRNAs (miRs) expression levels. The aims of our study were to investigate JAK2 V617F mutation allele burden and miR-143 expression levels in MPNs patients and to investigate the correlation between these genetic signatures and hematological parameters.
  
  
  METHODS
  In total 78 patients with a clinical diagnosis of polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IM), made according to the WHO 2008 criteria, were included in the study. Twenty healthy subjects were checked as controls. Quantification of JAK2 V617F mutation and miR-143 expression levels were determined by real-time quantitative polymerase chain reaction.
  
  
  RESULTS
  The miR-143 expression in MPNs patients was 2.97-fold higher than in controls. JAK2 V617F mutation allele burden and miR-143 expression level resulted higher in PV and IM respect to ET patients. Patients who had V617F allele burden >50% displayed a higher miRNA-143 expression level than patients with allele burden <50%. In MPNs patients, a statistically significant positive correlation was observed between JAK2 V617F mutation allele burden and hemoglobin and hematocrit values and between miR-143 expression levels and platelet count.
  
  
  CONCLUSIONS
  Our findings of aberrant miR-143 expression support the concept that factors other than JAK2 V617F mutation may contribute to the pathogenesis and some clinical signs of MPNs.
authors.forename: Marco
authors.initials: M
authors.lastname: Benati
authors.forename: Martina
authors.initials: M
authors.lastname: Montagnana
authors.forename: Elisa
authors.initials: E
authors.lastname: Danese
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Matteis
authors.forename: Dino
authors.initials: D
authors.lastname: Veneri
authors.forename: Elisa
authors.initials: E
authors.lastname: Paviati
authors.forename: Gian Cesare
authors.initials: GC
authors.lastname: Guidi
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D059645:Mutation Rate; D009196:Myeloproliferative Disorders / Q000097:blood / Q000201:enzymology* / Q000235:genetics*
chemical_list: C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D053614:Janus Kinase 2