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. 2015 Feb;135(2):272-80.
doi: 10.1016/j.thromres.2014.11.006. Epub 2014 Nov 15.

The JAK2 V617F mutational status and allele burden may be related with the risk of venous thromboembolic events in patients with Philadelphia-negative myeloproliferative neoplasms

Martyna Borowczyk  1 , Marzena Wojtaszewska  2 , Krzysztof Lewandowski  2 , Lidia Gil  2 , Maria Lewandowska  2 , Agata Lehmann-Kopydłowska  2 , Renata Kroll-Balcerzak  2 , Andrzej Balcerzak  2 , Małgorzata Iwoła  2 , Michał Michalak  3 , Mieczysław Komarnicki  2
Affiliations

The JAK2 V617F mutational status and allele burden may be related with the risk of venous thromboembolic events in patients with Philadelphia-negative myeloproliferative neoplasms

Martyna Borowczyk et al. Thromb Res. 2015 Feb.

Abstract

Introduction: Patients with Philadelphia-negative myeloproliferative neoplasms (Ph(-) MPNs) are at increased risk of thromboembolic and hemorrhagic complications. The aim of the study was to determine the relationship between JAK2 V617F mutational status, JAK2 V617F allele burden and the risk of vascular complications occurrence.

Materials and methods: Analysis was performed in a cohort of 186 patients diagnosed with polycythemia vera (53), essential thrombocythemia (114), primary myelofibrosis (11), and unclassified MPN (8). The risk of vascular complications development was analyzed in 126 JAK2 V617F-positive patients with respect to allele burden assessed with allele-specific 'real-time' quantitative polymerase chain reaction (AS RQ-PCR).

Results: Overall prevalence of any vascular complications was 44.6%. Arterial thrombosis occurred in 20.4%, venous thromboembolism (VTE) in 11.3%, bleeding episodes in 24.7% of patients. Individuals harboring JAK2 V617F mutation, regardless of MPN type, were at higher risk of VTE (OR=5.15, 95%CI: 1.16-22.90, P=0.024), mainly deep vein thrombosis (DVT). JAK2 allele burden higher than 20% identified patients with 7.4-fold increased risk of VTE (95%CI: 1.6-33.7, P=0.004), but not of arterial thrombosis, neither of bleeding complications, and remained the only significant VTE risk factor in multivariate logistic regression. High allele burdens (over 50%) were strikingly associated with proximal DVT cases, but not with distal DVT.

Conclusions: The group of MPN patients with JAK2 V617F allele burden higher than 20% may benefit the most from vigilant monitoring and appropriate prophylaxis against vascular events. Inclusion of JAK2 V617F mutant allele burden in new risk stratifications seems to be justified and requires controlled prospective trials.

Keywords: Hemorrhage; JAK 2; Myeloproliferative neoplasms; Quantitative real-time polymerase chain reaction; Thrombosis.

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Comment in

  • The JAK2 V617F mutational status and allele burden.
    Liang S, Zhou Y. Liang S, et al. Thromb Res. 2015 Sep;136(3):690. doi: 10.1016/j.thromres.2015.07.008. Epub 2015 Jul 13. Thromb Res. 2015. PMID: 26186962 No abstract available.
  • The JAK2 V617F mutational status and allele burden--authors' reply.
    Borowczyk M, Wojtaszewska M, Lewandowski K, Gil L, Lewandowska M, Lehmann-Kopydłowska A, Kroll-Balcerzak R, Balcerzak A, Iwoła M, Michalak M, Komarnicki M. Borowczyk M, et al. Thromb Res. 2015 Sep;136(3):691-2. doi: 10.1016/j.thromres.2015.07.006. Epub 2015 Jul 10. Thromb Res. 2015. PMID: 26216656 No abstract available.

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