title: JAK2V617F somatic mutation in the general population: myeloproliferative neoplasm development and progression rate.
abstract: Clinical significance of the JAK2V617F mutation in patients with a myeloproliferative neoplasm has been the target of intensive research in recent years. However, there is considerably uncertainty about prognosis in JAK2V617F positive individuals without overt signs of myeloproliferative disease. In this study, we tested the hypothesis that increased JAK2V617F somatic mutation burden is associated with myeloproliferative neoplasm progression rate in the general population. Among 49,488 individuals from the Copenhagen General Population Study, 63 (0.1%) tested positive for the JAK2V617F mutation in the time period 2003-2008. Of these, 48 were available for re-examination in 2012. Level of JAK2V617F mutation burden was associated with myeloproliferative neoplasm progression rate, consistent with a biological continuum of increasing JAK2V617F mutation burden across increasing severity of myeloproliferative neoplasm from no disease (n=8 at re-examination) through essential thrombocythemia (n=20) and polycythemia vera (n=13) to primary myelofibrosis (n=7). Among those diagnosed with a myeloproliferative neoplasm only at re-examination in 2012, in the preceding years JAK2V617F mutation burden increased by 0.55% per year, erythrocyte volume fraction increased by 1.19% per year, and erythrocyte mean corpuscular volume increased by 1.25% per year, while there was no change in platelet count or erythropoietin levels. Furthermore, we established a JAK2V617F mutation burden cut-off point of 2% indicative of disease versus no disease; however, individuals with a mutation burden below 2% may suffer from a latent form of myeloproliferative disease revealed by a slightly larger spleen and/or slightly higher lactic acid dehydrogenase concentration compared to controls. Of all 63 JAK2V617F positive individuals, 48 were eventually diagnosed with a myeloproliferative neoplasm.
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital Faculty of Health and Medical Sciences, University of Copenhagen.
authors.forename: Camilla
authors.initials: C
authors.lastname: Nielsen
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital Faculty of Health and Medical Sciences, University of Copenhagen.
authors.forename: Stig E
authors.initials: SE
authors.lastname: Bojesen
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital Faculty of Health and Medical Sciences, University of Copenhagen.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital Department of Cardiology, Rigshospitalet, Copenhagen University Hospital Department of Radiology, Rigshospitalet, Copenhagen University Hospital.
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Kofoed
authors.affiliation: Faculty of Health and Medical Sciences, University of Copenhagen Department of Hematology, Herlev Hospital, Copenhagen University Hospital, Denmark henrik.birgens@regionh.dk.
authors.forename: Henrik S
authors.initials: HS
authors.lastname: Birgens
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000473:pathology; D003718:Denmark / Q000453:epidemiology; D018450:Disease Progression; D004909:Erythrocyte Indices; D004921:Erythropoietin / Q000378:metabolism; D005260:Female; D005820:Genetic Testing; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D010976:Platelet Count; D011446:Prospective Studies; D012042:Registries; D012720:Severity of Illness Index
chemical_list: C554270:EPO protein, human; D004921:Erythropoietin; C507924:JAK2 protein, human; D053614:Janus Kinase 2