Frequency of JAK2V617F, MPL and CALR driver mutations and associated clinical characteristics in a Norwegian patient cohort with myeloproliferative neoplasms

Abstract

Myeloproliferative neoplasms are hematological disorders characterized by increased production in one or more myeloid cell lines, associated with driver mutations in JAK2-, MPL- and CALR-genes. The aims of this study were to investigate the prevalence of these driver mutations in a Norwegian patient cohort with myeloproliferative neoplasms, and to assess whether the different mutations were associated with different clinical presentation and natural history.

Results from 820 patients in whom analysis for JAK2V617F-, CALR- and MPL had been performed at Haukeland University Hospital in the period 2014-2019 were retrieved and analyzed together with clinical variables related to diagnosis, hematological blood parameters and complications, obtained from patient records.

We identified 182 cases of myeloproliferative neoplasms: 78 with JAK2V617F, 28 with CALR-mutations, two with MPL-mutations and 23 cases without a driver mutation. There was a lower prevalence of JAK2V617F mutation than expected in the polycythemia vera group, likely related to overdiagnosis. In patients with essential thrombocytosis, we found significantly higher levels of hemoglobin and erythrocyte volume fraction for JAK2V617F-mutated disease, and significantly higher levels of platelets and lactate dehydrogenase for CALR-mutated disease. Patients with JAK2V617F-mutated primary myelofibrosis had significantly higher levels of hemoglobin, and there was an increased number of smokers or former smokers in this group compared to patients with CALR-mutations.

Except for a lower prevalence of JAK2V617F-mutation in polycythemia vera, the mutational distribution in our patient cohort was similar to previous findings in other populations. The novel finding of a higher prevalence of smokers in JAK2V617F-mutated primary myelofibrosis warrants further investigation.

Keywords:

• JAK2
• CALR
• MPL
• essential thrombocytosis
• primary myelofibrosis
• polycytemia vera
• smokers

Author contributions

All authors participated in this study including data interpretation and manuscript preparation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors thank the support for research on blood diseases from Western Norway Regional Health Authority, the Caroline Museæus Aarsvolds fund, the Norwegian Society of Internal medicine, Rotary, the Rakel and Otto Kristian Bruun grant and Eivind Mølbach Petersens fund.