title: JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes.
abstract: Patients with essential thrombocythemia may carry JAK2 (V617F), an MPL substitution, or a calreticulin gene (CALR) mutation. We studied biologic and clinical features of essential thrombocythemia according to JAK2 or CALR mutation status and in relation to those of polycythemia vera. The mutant allele burden was lower in JAK2-mutated than in CALR-mutated essential thrombocythemia. Patients with JAK2 (V617F) were older, had a higher hemoglobin level and white blood cell count, and lower platelet count and serum erythropoietin than those with CALR mutation. Hematologic parameters of patients with JAK2-mutated essential thrombocythemia or polycythemia vera were related to the mutant allele burden. While no polycythemic transformation was observed in CALR-mutated patients, the cumulative risk was 29% at 15 years in those with JAK2-mutated essential thrombocythemia. There was no significant difference in myelofibrotic transformation between the 2 subtypes of essential thrombocythemia. Patients with JAK2-mutated essential thrombocythemia and those with polycythemia vera had a similar risk of thrombosis, which was twice that of patients with the CALR mutation. These observations are consistent with the notion that JAK2-mutated essential thrombocythemia and polycythemia vera represent different phenotypes of a single myeloproliferative neoplasm, whereas CALR-mutated essential thrombocythemia is a distinct disease entity.
authors.affiliation: Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy;
authors.forename: Elisa
authors.initials: E
authors.lastname: Rumi
authors.forename: Daniela
authors.initials: D
authors.lastname: Pietra
authors.forename: Virginia
authors.initials: V
authors.lastname: Ferretti
authors.forename: Thorsten
authors.initials: T
authors.lastname: Klampfl
authors.forename: Ashot S
authors.initials: AS
authors.lastname: Harutyunyan
authors.forename: Jelena D
authors.initials: JD
authors.lastname: Milosevic
authors.forename: Nicole C C
authors.initials: NC
authors.lastname: Them
authors.forename: Tiina
authors.initials: T
authors.lastname: Berg
authors.forename: Chiara
authors.initials: C
authors.lastname: Elena
authors.forename: Ilaria C
authors.initials: IC
authors.lastname: Casetti
authors.forename: Chiara
authors.initials: C
authors.lastname: Milanesi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Sant'antonio
authors.forename: Marta
authors.initials: M
authors.lastname: Bellini
authors.forename: Elena
authors.initials: E
authors.lastname: Fugazza
authors.forename: Maria C
authors.initials: MC
authors.lastname: Renna
authors.forename: Emanuela
authors.initials: E
authors.lastname: Boveri
authors.forename: Cesare
authors.initials: C
authors.lastname: Astori
authors.forename: Cristiana
authors.initials: C
authors.lastname: Pascutto
authors.forename: Robert
authors.initials: R
authors.lastname: Kralovics
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D037282:Calreticulin / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003062:Codon; D005091:Exons; D005260:Female; D006098:Granulocytes; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics; D011087:Polycythemia Vera / Q000235:genetics; D055728:Primary Myelofibrosis / Q000235:genetics; D011379:Prognosis; D053628:Receptors, Thrombopoietin / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D013927:Thrombosis / Q000235:genetics; D055815:Young Adult
chemical_list: D037282:Calreticulin; D003062:Codon; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D053614:Janus Kinase 2