title: Calreticulin mutations and long-term survival in essential thrombocythemia.
abstract: The impact of calreticulin (CALR) mutations on long-term survival in essential thrombocythemia (ET) was examined in 299 patients whose diagnosis predated 2006. Mutational frequencies were 53% for Janus kinase 2 (JAK2), 32% for CALR and 3% for MPL; the remaining 12% were 'triple-negative'. We confirmed the association of mutant CALR (vs JAK2V617F) with younger age (P=0.002), male sex (P=0.01), higher platelet count (0.0004), lower hemoglobin (P<0.0001), lower leukocyte count (0.02) and lower incidence of recurrent thrombosis (0.04). Triple-negative patients were also younger than their JAK2-mutated counterparts (P=0.003) and displayed lower hemoglobin (P=0.003), lower leukocyte count (<0.0001) and lower thrombotic events (P=0.02). Median follow-up time was 12.7 years and 47% of the patients were followed until death. Survival was the longest for triple-negative and shortest for MPL-mutated patients. Median survival was 19 years for JAK2 and 20 years for CALR-mutated cases (P=0.32); the corresponding figures for patients of age ⩽65 years were 26 and 32 years (P=0.56). The two mutational categories were also similar for leukemic (P=0.28) and fibrotic (P=0.28) progression rates. The current study is uniquely characterized by its very long follow-up period and provides accurate estimates of long-term survival in ET and complements current information on mutation-specific phenotype and prognosis.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Wassie
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Lasho
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: C
authors.initials: C
authors.lastname: Finke
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Belachew
authors.affiliation: Division of Cytogenetics, Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Ketterling
authors.affiliation: Division of Hematopathology, Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Hanson
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pardanani
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: N
authors.initials: N
authors.lastname: Gangat
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Wolanskyj
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D037282:Calreticulin / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D053628:Receptors, Thrombopoietin / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D055815:Young Adult
chemical_list: D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2