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Prevalence and phenotypes of JAK2 V617F and Calreticulin mutations in a Danish general population

Sabrina Cordua, Lasse Kjaer, Vibe Skov, Niels Pallisgaard, Hans C. Hasselbalch and Christina Ellervik

Key Points

  • CALR mutations are prevalent in the general population but are much less frequent compared to the estimated JAK2 V617F prevalence

  • JAK2 V617F and CALR mutations in the general population are linked to a distinct blood count profile, also in the absence of MPN diagnosis

Abstract

The JAK2 V617F and Calreticulin mutations (CALR) are frequent driver mutations within the myeloproliferative neoplasms (MPN). JAK2 V617F has been detected in the general population but no studies have previously investigated the prevalence of CALR. Thus, we aimed to determine the CALR and JAK2 V617F population prevalence and to assess the biochemical profile and lifestyle risk factors in mutation positives with and without MPN. 19,958 eligible participants, enrolled from 2010-2013, from the Danish General Suburban Population Study including DNA, blood tests, and questionnaires were screened for JAK2 V617F and CALR by droplet digital PCR. 645 participants were mutation positive (3.5%) and 16 of these (2.5%) had MPN at baseline. 613 participants were JAK2 V617F positive (allele burden (mean(SE)):2.1(0.34)%) and 32 participants were CALR positive (allele burden:7.5(2.2)%), corresponding to a population prevalence of 3.1% (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=1.6x10-10). Mutation positives displayed higher blood cell counts compared to non-mutated, and 40% of mutation positives without MPN presented elevation of {greater than or equal to}1 blood cell counts. In conclusion, we present a novel population prevalence of CALR and a JAK2 V617F prevalence that is 3-30 times higher compared to less sensitive methods. Mutation positive non-MPNs have elevated blood cell counts which raises concerns of underdiagnosis of MPN in the population.

  • Submitted January 3, 2019.
  • Revision received June 14, 2019.
  • Accepted June 12, 2019.