title: Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis.
abstract: Janus kinase 2 (JAK2) mutations define polycythemia vera (PV). Calreticulin (CALR) and myeloproliferative leukemia virus oncogene (MPL) mutations are specific to JAK2-unmutated essential thrombocythemia (ET) and primary myelofibrosis (PMF). We examined the effect of these mutations on long-term disease outcome. One thousand five hundred eighty-one patients from the Mayo Clinic (n = 826) and Italy (n = 755) were studied. Fifty-eight percent of Mayo patients were followed until death; median survivals were 19.8 years in ET (n = 292), 13.5 PV (n = 267; hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.4-2.2), and 5.9 PMF (n = 267; HR, 4.5; 95% CI, 3.5-5.7). The survival advantage of ET over PV was not affected by JAK2/CALR/MPL mutational status. Survival in ET was inferior to the age- and sex-matched US population (P < .001). In PMF (n = 428), but not in ET (n = 576), survival and blast transformation (BT) were significantly affected by mutational status; outcome was best in CALR-mutated and worst in triple-negative patients: median survival, 16 vs 2.3 years (HR, 5.1; 95% CI, 3.2-8.0) and BT, 6.5% vs 25% (HR, 7.6; 95% CI, 2.8-20.2), respectively. We conclude that life expectancy in morphologically defined ET is significantly reduced but remains superior to that of PV, regardless of mutational status. In PMF, JAK2/CALR/MPL mutational status is prognostically informative.
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN;
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
authors.affiliation: Laboratorio Congiunto MMPC, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy;
authors.forename: Paola
authors.initials: P
authors.lastname: Guglielmelli
authors.affiliation: Department of Statistics and Bioinformatics.
authors.forename: Dirk R
authors.initials: DR
authors.lastname: Larson
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN;
authors.forename: Christy
authors.initials: C
authors.lastname: Finke
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN;
authors.forename: Emnet A
authors.initials: EA
authors.lastname: Wassie
authors.affiliation: Laboratorio Congiunto MMPC, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy;
authors.forename: Lisa
authors.initials: L
authors.lastname: Pieri
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN;
authors.forename: Naseema
authors.initials: N
authors.lastname: Gangat
authors.affiliation: Laboratorio Congiunto MMPC, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy;
authors.forename: Rajmonda
authors.initials: R
authors.lastname: Fjerza
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN;
authors.forename: Alem A
authors.initials: AA
authors.lastname: Belachew
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN;
authors.forename: Terra L
authors.initials: TL
authors.lastname: Lasho
authors.affiliation: Division of Cytogenetics, Department of Laboratory Medicine, and.
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.affiliation: Division of Hematopathology, Department of Laboratory Medicine, Mayo Clinic, Rochester, MN;
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.affiliation: Division of Hematology and Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy; and.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.affiliation: Division of Hematology and Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy; and.
authors.forename: Guido
authors.initials: G
authors.lastname: Finazzi
authors.affiliation: Institute of Pathology, University of Cologne, Cologne, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Thiele
authors.affiliation: Division of Hematology and Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy; and.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN;
authors.forename: Animesh
authors.initials: A
authors.lastname: Pardanani
authors.affiliation: Laboratorio Congiunto MMPC, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy;
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*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011087:Polycythemia Vera / Q000175:diagnosis / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D016019:Survival Analysis; D013920:Thrombocythemia, Essential / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2