title: Mutations and thrombosis in essential thrombocythemia: prognostic interaction with age and thrombosis history.
abstract: BACKGROUND
  Vascular events in essential thrombocythemia (ET) are associated with advanced age and thrombosis history. Recent information suggests additional effect from the presence of specific mutations.
  
  
  OBJECTIVE
  To examine the influence of age and thrombosis history on the reported association between mutational status and thrombosis-free survival in ET.
  
  
  METHODS
  Analysis was performed using a Mayo Clinic cohort of 300 ET patients, and key findings were reanalyzed by including additional 102 Italian patients.
  
  
  RESULTS
  Among 300 Mayo patients with ET (median age 55 yr, 60% females), mutational frequencies were 53% JAK2, 32% CALR, 3% MPL, and 12% JAK2, CALR and MPL wild type. One hundred and six (35%) patients experienced arterial (n = 75) or venous (n = 43) events, before (n = 55) or after (n = 71) diagnosis. In univariate analysis, compared to JAK2-mutated cases, JAK2, CALR and MPL wild type (HR 0.31, 95% CI 0.11-0.86), and CALR-mutated (0.53, 95% CI 0.30-0.92) patients displayed better thrombosis-free survival. JAK2, CALR, and MPL wild type remained significant (P = 0.03; HR 0.32, 95% CI 0.11-0.9) during multivariable analysis that included age (P = 0.01) and thrombosis history (P = 0.0006); a favorable impact from CALR mutations was of borderline significance (P = 0.1; HR 0.62, 95% CI 0.35-1.1), but became significant (P = 0.02) when multivariable analysis including thrombosis history (P = 0.02) was performed on patients younger than 60 yr of age.
  
  
  CONCLUSIONS
  The favorable impact of mutational status on thrombosis-free survival in ET might be most evident for JAK2, CALR, and MPL wild type patients, whereas the favorable effect from CALR mutations might be confined to young patients.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Naseema
authors.initials: N
authors.lastname: Gangat
authors.forename: Emnet A
authors.initials: EA
authors.lastname: Wassie
authors.forename: Terra L
authors.initials: TL
authors.lastname: Lasho
authors.forename: Christy
authors.initials: C
authors.lastname: Finke
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.forename: Animesh
authors.initials: A
authors.lastname: Pardanani
authors.forename: Alexandra P
authors.initials: AP
authors.lastname: Wolanskyj
authors.forename: Margherita
authors.initials: M
authors.lastname: Maffioli
authors.forename: Rosario
authors.initials: R
authors.lastname: Casalone
authors.forename: Francesco
authors.initials: F
authors.lastname: Passamonti
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D037282:Calreticulin / Q000235:genetics; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D053628:Receptors, Thrombopoietin / Q000235:genetics; D012307:Risk Factors; D013920:Thrombocythemia, Essential / Q000150:complications* / Q000235:genetics* / Q000401:mortality; D013927:Thrombosis / Q000209:etiology*; D055815:Young Adult
chemical_list: D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D053614:Janus Kinase 2
keywords: calreticulin; essential thrombocythemia; janus kinase 2; mutation; thrombosis