Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec;193(6):2883-2888.
doi: 10.1007/s11845-024-03776-5. Epub 2024 Aug 14.

Association between JAK2V617F variable allele frequency and risk of thrombotic events in patients with myeloproliferative neoplasms

Ryan Brown  1 , Joanna Jasiakiewicz  1 , Victoria Greer  1 , Andrew Hindley  1 , Katie McDowell  1 , Eadaoin Devlin  1 , Kathryn Clarke  1 , Frances Buckley  2 , Clare Crean  1 , Julie McGimpsey  1 , Robert J G Cuthbert  1 , Nick Cunningham  1 , Claire Arnold  1 , Damian Finnegan  1 , Gary Benson  1 , Mary Frances McMullin  3   4 , Mark A Catherwood  1
Affiliations

Association between JAK2V617F variable allele frequency and risk of thrombotic events in patients with myeloproliferative neoplasms

Ryan Brown et al. Ir J Med Sci. 2024 Dec.

Abstract

Background: Myeloproliferative neoplasms (MPNs) are a group of chronic disorders of the bone marrow characterised by the overproduction of clonal myeloid stem cells. The most common driver mutation found in MPNs is a point mutation on exon 14 of the JAK2 gene, JAK2V617F. Various studies have suggested that measuring the variable allele frequency (VAF) of JAK2V617F may provide useful insight regarding diagnosis, treatment, risks and outcomes in MPN patients. In particular, JAK2V617F has been associated with increased risk of thrombotic events, a leading cause of mortality in MPNs.

Aims: The aim of this study was to determine if JAK2V617F VAF was associated with clinical outcomes in patients with MPN.

Methods: JAK2V617F VAF was determined by quantitative PCR (qPCR) in a cohort of 159 newly diagnosed MPN patients, and the association of JAK2V617F VAF and risk of thrombosis was examined in this cohort.

Results: We observed a significantly higher JAK2V617F VAF in PV and PMF versus ET. A significant association was observed between JAK2V617F VAF and risk of thrombotic events. When patients were stratified by thrombotic events prior to and post diagnosis, an association with JAK2V617F VAF was only observed with post diagnosis thrombotic events. Of note, these associations were not observed when looking at each MPN subtype in isolation.

Conclusions: We have shown that a higher JAK2V617F VAF is associated with thrombotic events post MPN diagnosis. JAK2V617F VAF may therefore provide a valuable prognostic indicator for risk of thrombosis in MPNs.

Keywords: JAK2; Myeloproliferative neoplasm; Thrombosis; Variable allele frequency.

PubMed Disclaimer

Conflict of interest statement

Declarations. Patient Consent: Not required. Provence and Peer review: Not commissioned; externally peer reviewed. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Comparison of JAK2V617F variant allele frequency (VAF) between a all cases, b polycythaemia vera (PV) cases, and c essential thrombocythaemia (ET) cases with, and without thrombotic events. n = 22–103 per group. *P < 0.05
Fig. 2
Fig. 2
Comparison of JAK2V617F VAF between a, d all cases, b, e polycythaemia vera (PV) cases and c, f essential thrombocythaemia (ET) cases with thrombotic events prior to (a–c) or post (d–f) diagnosis. n = 2–143 per group, *P < 0.05
See this image and copyright information in PMC

References

    1. Rolles B, Mullally A (2022) Molecular pathogenesis of myeloproliferative neoplasms. Curr Hematol Malig Rep [Internet]. [cited 2023 Sep 20];17(6):319–29. Available from: https://link.springer.com/article/10.1007/s11899-022-00685-1 - DOI - PubMed
    1. Thiele J, Kvasnicka HM, Orazi A et al. (2023) The international consensus classification of myeloid neoplasms and acute Leukemias: myeloproliferative neoplasms. Am J Hematol [Internet]. [cited 2023 Sep 20];98(1):166–79. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.26751 - DOI - PubMed
    1. Khoury JD, Solary E, Abla O et al. (2022 ) The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia 2022 36:7 [Internet]. [cited 2023 Sep 20];36(7):1703–19. Available from: https://www.nature.com/articles/s41375-022-01613-1 - PMC - PubMed
    1. Greenfield G, McMullin MF, Mills K (2021) Molecular pathogenesis of the myeloproliferative neoplasms. J Hematol Oncol 2021 14:1 [Internet]. [cited 2023 Sep 20];14(1):1–18. Available from: https://jhoonline.biomedcentral.com/articles/10.1186/s13045-021-01116-z - DOI - PMC - PubMed
    1. Moliterno AR, Kaizer H, Reeves BN (2023) JAK2V617F allele burden in polycythemia vera: burden of proof. Blood [Internet]. [cited 2023 Sep 20];141(16):1934–42. Available from: 10.1182/blood.2022017697 - PMC - PubMed

LinkOut - more resources