title: [JAK2-V617F mutation in patients with myeloproliferative neoplasms: association with FLT3-ITD mutation].
abstract: BACKGROUND
  An acquired somatic mutation V617F in Janus kinase 2 gene (JAK2) is the cause of uncontrolled proliferation in patients with myeloproliferative neoplasms. It is known that uncontrolled myeloid cell proliferation is also provoked by alteration in other genes, e.g. mutations in receptor tyrosine kinase FLT3 gene. FLT3 represents the most frequently mutated gene in acute myeloid leukaemia. Interestingly, mutated FLT3-ITD (internal tandem duplication) protein is a member of the same signalling pathway as JAK2 protein, the STATS signalling pathway. STAT5 activation is recognized as important for self-renewal of haematopoetic stem cells.
  
  
  OBJECTIVE
  The aim of this study was the detection of JAK2-V617F mutation in patients with myeloproliferative neoplasms. Additionally, we investigated the presence of FLT3-ITD mutation in JAK2-V617F-positive patients in order to shed the light on the hypothesis of a similar role of these two molecular markers in haematological malignancies.
  
  
  METHODS
  Using allele-specific PCR, 61 patients with known or suspected diagnosis of myeloproliferative neoplasms were tested for the presence of JAK2-V617F mutation. Samples that were positive for JAK2 mutation were subsequently tested for the presence of FLT3-ITD mutation by PCR.
  
  
  RESULTS
  Eighteen of 61 analysed patients were positive for JAK2-V617F mutation. Among them, 8/18 samples were diagnosed as polycythaemia vera, and 10/18 as essential thrombocythaemia. None of JAK2-V617F-positive patient was positive for FLT3-ITD mutation.
  
  
  CONCLUSIONS
  This study suggests that one activating mutation is sufficient for aberrant cell proliferation leading to malignant transformation of haematopoetic stem cell.
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Spasovski
authors.forename: Natasa
authors.initials: N
authors.lastname: Tosić
authors.forename: Tatjana
authors.initials: T
authors.lastname: Kostić
authors.forename: Sonja
authors.initials: S
authors.lastname: Pavlović
authors.forename: Milica
authors.initials: M
authors.lastname: Colović
mesh_terms: D049109:Cell Proliferation; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D053614:Janus Kinase 2