title: Primary myelofibrosis with or without mutant MPL: comparison of survival and clinical features involving 603 patients.
abstract: MPL and JAK2V617F mutation analysis was performed in 603 patients with primary myelofibrosis (PMF) seen at the Mayo Clinic, USA (n=329) or University of Florence, Italy (n=274). Mutant MPL was detected in 49 (8.1%) patients and JAK2V617F in 350 (58%); 4 patients showed both mutations. MPLW515L/K was the commonest mutation; 2 patients showed novel mutations (L513ins and Q516-P518insAAAA). The US and Italy patient cohorts were separately analyzed for comparison of survival and clinical features between MPL-mutated, JAK2-mutated and JAK2/MPL-unmutated cases. JAK2/MPL-unmutated patients were significantly younger than their JAK2-mutated counterparts, in both patient cohorts (P<0.01). In the Florence only cohort, the presence of mutant MPL was associated with older age (P<0.01) and constitutional symptoms (P=0.04) and JAK2V617F with higher hemoglobin (P<0.01) and leukocyte (P=0.03) count; neither patient cohort showed significant associations with platelet count, hemoglobin <10 g/dl, abnormal/unfavorable karyotype, spleen size or prognostic score distribution. To date, 240 deaths and 79 leukemic transformations have been documented among all 603 study patients. Multivariable analysis disclosed no significant difference in overall or leukemia-free survival between the three molecular subgroups. We conclude that the presence of mutant MPL has narrow and inconsistent phenotypic effect in PMF and does not influence overall or leukemia-free survival.
authors.affiliation: Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pardanani
authors.forename: P
authors.initials: P
authors.lastname: Guglielmelli
authors.forename: T L
authors.initials: TL
authors.lastname: Lasho
authors.forename: A
authors.initials: A
authors.lastname: Pancrazzi
authors.forename: C M
authors.initials: CM
authors.lastname: Finke
authors.forename: A M
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy; D053614:Janus Kinase 2 / Q000235:genetics; D059785:Karyotype; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D015996:Survival Rate; D014481:United States; D055815:Young Adult
chemical_list: D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2