title: CALR exon 9 mutations are somatically acquired events in familial cases of essential thrombocythemia or primary myelofibrosis.
abstract: Somatic mutations in the calreticulin (CALR) gene were recently discovered in patients with sporadic essential thrombocythemia (ET) and primary myelofibrosis (PMF) lacking JAK2 and MPL mutations. We studied CALR mutation status in familial cases of myeloproliferative neoplasm. In a cohort of 127 patients, CALR indels were identified in 6 of 55 (11%) subjects with ET and in 6 of 20 (30%) with PMF, whereas 52 cases of polycythemia vera had nonmutated CALR. All CALR mutations were somatic, found in granulocytes but not in T lymphocytes. Patients with CALR-mutated ET showed a higher platelet count (P = .017) and a lower cumulative incidence of thrombosis (P = .036) and of disease progression (P = .047) compared with those with JAK2 (V617F). In conclusion, a significant proportion of familial ET and PMF nonmutated for JAK2 carry a somatic mutation of CALR.
authors.affiliation: Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy;
authors.forename: Elisa
authors.initials: E
authors.lastname: Rumi
authors.forename: Ashot S
authors.initials: AS
authors.lastname: Harutyunyan
authors.forename: Daniela
authors.initials: D
authors.lastname: Pietra
authors.forename: Jelena D
authors.initials: JD
authors.lastname: Milosevic
authors.forename: Ilaria C
authors.initials: IC
authors.lastname: Casetti
authors.forename: Marta
authors.initials: M
authors.lastname: Bellini
authors.forename: Nicole C C
authors.initials: NC
authors.lastname: Them
authors.forename: Chiara
authors.initials: C
authors.lastname: Cavalloni
authors.forename: Virginia V
authors.initials: VV
authors.lastname: Ferretti
authors.forename: Chiara
authors.initials: C
authors.lastname: Milanesi
authors.forename: Tiina
authors.initials: T
authors.lastname: Berg
authors.forename: Emanuela
authors.initials: E
authors.lastname: Sant'Antonio
authors.forename: Emanuela
authors.initials: E
authors.lastname: Boveri
authors.forename: Cristiana
authors.initials: C
authors.lastname: Pascutto
authors.forename: Cesare
authors.initials: C
authors.lastname: Astori
authors.forename: Robert
authors.initials: R
authors.lastname: Kralovics
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D037282:Calreticulin / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D053208:Kaplan-Meier Estimate; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D055728:Primary Myelofibrosis / Q000235:genetics* / Q000401:mortality; D013920:Thrombocythemia, Essential / Q000235:genetics* / Q000401:mortality
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; C507924:JAK2 protein, human; D053614:Janus Kinase 2