title: Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia.
abstract: Mutations in the calreticulin (CALR) gene were recently discovered in patients with essential thrombocythemia (ET) lacking the JAK2V617F and MPLW515 mutations, but no information is available on the clinical correlates. In this series, CALR mutations were found in 15.5% of 576 World Health Organization-defined ET patients, accounting for 48.9% of JAK2 and MPL wild-type (wt) patients. CALR-mutated patients were preferentially male and showed higher platelet count and lower hemoglobin and leukocyte count compared with JAK2- and MPL-mutated patients. Patients carrying the CALR mutation had a lower risk of thrombosis than JAK2- and MPL-mutated patients; of interest, their risk was superimposable to patients who were wt for the above mutations. CALR mutation had no impact on survival or transformation to post-ET myelofibrosis. Genotyping for CALR mutations represents a novel useful tool for establishing a clonal myeloproliferative disorder in JAK2 and MPL wt patients with thrombocytosis and may have prognostic and therapeutic relevance.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence; and Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.
authors.forename: Giada
authors.initials: G
authors.lastname: Rotunno
authors.forename: Carmela
authors.initials: C
authors.lastname: Mannarelli
authors.forename: Paola
authors.initials: P
authors.lastname: Guglielmelli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pacilli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pancrazzi
authors.forename: Lisa
authors.initials: L
authors.lastname: Pieri
authors.forename: Tiziana
authors.initials: T
authors.lastname: Fanelli
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; D037282:Calreticulin / Q000235:genetics*; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D015995:Prevalence; D011379:Prognosis; D000071156:Promyelocytic Leukemia Protein; D016019:Survival Analysis; D013920:Thrombocythemia, Essential / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D037282:Calreticulin; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D053614:Janus Kinase 2