TY - JOUR
T1 - Prevalence and phenotypes of JAK2 V617F and calreticulin mutations in a Danish general population
AU - Cordua, Sabrina
AU - Kjaer, Lasse
AU - Skov, Vibe
AU - Pallisgaard, Niels
AU - Hasselbalch, Hans C.
AU - Ellervik, Christina
PY - 2019/8/1
Y1 - 2019/8/1
N2 - The JAK2 V617F and calreticulin mutations (CALR) are frequent within myeloproliferative neoplasms (MPNs). JAK2 V617F has been detected in the general population, but no studies have previously investigated the CALR prevalence. Thus, we aimed to determine the CALR and JAK2 V617F population prevalence and assess the biochemical profile and lifestyle factors in mutation-positive individuals with and without MPN. 19 958 eligible participants, enrolled from 2010-2013, from the Danish General Suburban Population Study were screened for JAK2 V617F and CALR by droplet digital polymerase chain reaction with (3.2%) mutation positives of which 16 (2.5%) had MPN at baseline. Of 645 participants, 613 were JAK2 V617F positive, and 32 were CALR positive, corresponding to a population prevalence of 3.1% (confidence interval [CI], 2.8-3.3) and 0.16% (CI, 0.11-0.23), respectively. Increasing age, smoking, and alcohol were risk factors for the mutations. JAK2 V617F positives with and without MPN presented elevated odds for prevalent venous thromboembolism. The odds ratio for a diagnosis of MPN per percentage allele burden was 1.14 (95% CI, 1.09-1.18; P 5 1.6 3 10210). Mutation positives displayed higher blood cell counts than nonmutated participants, and 42% of mutation positives without MPN presented elevation of ‡1 blood cell counts; 80 (13%) even presented blood cell counts in accordance with current MPN diagnostic criteria. In conclusion, we present a novel population prevalence of CALR and a JAK2 V617F prevalence that is 3 to 30 times higher compared with less sensitive methods. Mutation-positive non-MPNs with elevated blood cell counts raise concerns of MPN underdiagnosis in the population.
AB - The JAK2 V617F and calreticulin mutations (CALR) are frequent within myeloproliferative neoplasms (MPNs). JAK2 V617F has been detected in the general population, but no studies have previously investigated the CALR prevalence. Thus, we aimed to determine the CALR and JAK2 V617F population prevalence and assess the biochemical profile and lifestyle factors in mutation-positive individuals with and without MPN. 19 958 eligible participants, enrolled from 2010-2013, from the Danish General Suburban Population Study were screened for JAK2 V617F and CALR by droplet digital polymerase chain reaction with (3.2%) mutation positives of which 16 (2.5%) had MPN at baseline. Of 645 participants, 613 were JAK2 V617F positive, and 32 were CALR positive, corresponding to a population prevalence of 3.1% (confidence interval [CI], 2.8-3.3) and 0.16% (CI, 0.11-0.23), respectively. Increasing age, smoking, and alcohol were risk factors for the mutations. JAK2 V617F positives with and without MPN presented elevated odds for prevalent venous thromboembolism. The odds ratio for a diagnosis of MPN per percentage allele burden was 1.14 (95% CI, 1.09-1.18; P 5 1.6 3 10210). Mutation positives displayed higher blood cell counts than nonmutated participants, and 42% of mutation positives without MPN presented elevation of ‡1 blood cell counts; 80 (13%) even presented blood cell counts in accordance with current MPN diagnostic criteria. In conclusion, we present a novel population prevalence of CALR and a JAK2 V617F prevalence that is 3 to 30 times higher compared with less sensitive methods. Mutation-positive non-MPNs with elevated blood cell counts raise concerns of MPN underdiagnosis in the population.
U2 - 10.1182/blood.2019001113
DO - 10.1182/blood.2019001113
M3 - Journal article
C2 - 31217187
AN - SCOPUS:85070740413
SN - 0006-4971
VL - 134
SP - 469
EP - 479
JO - Blood
JF - Blood
IS - 5
ER -