JAK2V617F variant allele frequency, non-driver mutations, single-nucleotide variants and polycythemia vera outcome

Zuzanna Kanduła; Michał Janowski; Barbara Więckowska; Edyta Paczkowska; Krzysztof Lewandowski

doi:10.1007/s00432-022-04327-0

JAK2V617F variant allele frequency, non-driver mutations, single-nucleotide variants and polycythemia vera outcome

J Cancer Res Clin Oncol. 2023 Jul;149(8):4789-4803. doi: 10.1007/s00432-022-04327-0. Epub 2022 Oct 15.

Authors

Zuzanna Kanduła¹, Michał Janowski², Barbara Więckowska³, Edyta Paczkowska², Krzysztof Lewandowski⁴

Affiliations

¹ Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland. zuzannakandula@gmail.com.
² Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
³ Department of Computer Science and Statistics, Poznań University of Medical Sciences, Poznań, Poland.
⁴ Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland.

Abstract

Introduction: Despite comparatively favourable prognosis in polycythemia vera (PV) patients (pts), the overall survival is shorter compared to the age-matched general population. The aim of the study was to evaluate the impact of chosen laboratory and genetic factors on the individual disease outcome, i.e. risk of thrombosis, myelofibrosis/blastic transformation and death.

Materials and methods: The study group consisted of 151 pts and 57 healthy donors (HD).

Results: JAK2V617F mutation was found in 96.7% (146/151) of the studied pts. JAK2 exon 12 mutations were identified in 2 individuals. The coexistence of JAK2V617F and JAK2 exon 12 mutation was confirmed in 2 other pts. In one case, neither JAK2V617F nor JAK2 exon 12 mutation was found. The presence of ten different non-driver mutations (ASXL1, SRSF2, U2AF1, IDH2) in eight of the analyzed pts (5.3%) was confirmed. The overall frequency of thrombotic events (TE) in the studied PV group was 23.8% (36/151). In patients with TE, median platelet count was lower than in pts without TE. Thrombotic risk did not depend on JAK2 rs12343867, TERT rs2736100, OBFC1 rs9420907 SNV, however, we found a novel strong tendency towards statistical significance between the CC genotype miR-146a rs2431697 and thrombosis. The disease progression to fibrotic phase was confirmed in 9% of the pts. Fibrotic transformation in PV pts was affected mainly by JAK2V617F variant allele frequency (VAF) and the presence of coexisting non-driver variants. The high JAK2V617F VAF and elevated white blood cell (WBC) count at the time of diagnosis were associated with an increased risk of death.

Conclusion: Therefore, in our opinion, complex, laboratory and genetic PV pts evaluation at the time of diagnosis should be incorporated into a new prognostic scoring system to more precisely define the PV prognosis and to optimize the therapeutic decision-making process.

Keywords: Blastic transformation risk; Death risk; JAK2V617F VAF; Myelofibrosis free survival; Polycythemia vera; Thrombosis.

MeSH terms

Gene Frequency
Humans
Janus Kinase 2 / genetics
Mutation
Nucleotides / therapeutic use
Polycythemia Vera* / diagnosis
Polycythemia Vera* / drug therapy
Polycythemia Vera* / genetics
Thrombosis* / genetics

Substances

Janus Kinase 2
Nucleotides