title: The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils from patients with polycythemia vera.
abstract: BACKGROUND
  The JAK2V617F mutation has been associated with constitutive and enhanced activation of neutrophils, while no information is available concerning other leukocyte subtypes.
  
  
  METHODS
  We evaluated correlations between JAK2V617F mutation and the count of circulating basophils, the number of activated CD63(+) basophils, their response in vitro to agonists as well as the effects of a JAK2 inhibitor.
  
  
  RESULTS
  We found that basophil count was increased in patients with JAK2V617F -positive myeloproliferative neoplasms, particularly in those with polycythemia vera, and was correlated with the V617F burden. The burden of V617F allele was similar in neutrophils and basophils from patients with polycythemia vera, while total JAK2 mRNA content was remarkably greater in the basophils; however, the content of JAK2 protein in basophils was not increased. The number of CD63(+) basophils was higher in patients with polycythemia vera than in healthy subjects or patients with essential thrombocythemia or primary myelofibrosis and was correlated with the V617F burden. Ultrastructurally, basophils from patients with polycythemia vera contained an increased number of granules, most of which were empty suggesting cell degranulation in vivo. Ex vivo experiments revealed that basophils from patients with polycythemia vera were hypersensitive to the priming effect of interleukin-3 and to f-MLP-induced activation; pre-treatment with a JAK2 inhibitor reduced polycythemia vera basophil activation. Finally, we found that the number of circulating CD63(+) basophils was significantly greater in patients suffering from aquagenic pruritus, who also showed a higher V617F allele burden.
  
  
  CONCLUSIONS
  These data indicate that the number of constitutively activated and hypersensitive circulating basophils is increased in polycythemia vera, underscoring a role of JAK2V617F in these cells' abnormal function and, putatively, in the pathogenesis of pruritus.
authors.affiliation: Unità Funzionale di Ematologia, Dipartimento di Area Critica, Università degli Studi, Firenze, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Pieri
authors.forename: Costanza
authors.initials: C
authors.lastname: Bogani
authors.forename: Paola
authors.initials: P
authors.lastname: Guglielmelli
authors.forename: Maria
authors.initials: M
authors.lastname: Zingariello
authors.forename: Rosa Alba
authors.initials: RA
authors.lastname: Rana
authors.forename: Niccolò
authors.initials: N
authors.lastname: Bartalucci
authors.forename: Alberto
authors.initials: A
authors.lastname: Bosi
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001491:Basophils / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011087:Polycythemia Vera / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D011537:Pruritus / Q000209:etiology; D055815:Young Adult
chemical_list: D053614:Janus Kinase 2