All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the MPN Advocates Network.
Introducing
Now you can personalise
your MPN Hub experience!
Bookmark content to read later
Select your specific areas of interest
View content recommended for you
Find out moreThe MPN Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the MPN Hub cannot guarantee the accuracy of translated content. The MPN Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
The MPN Hub is an independent medical education platform, sponsored by AOP Health and GSK, and supported through an educational grant from Bristol Myers Squibb. The funders are allowed no direct influence on our content. The levels of sponsorship listed are reflective of the amount of funding given. View funders.
Bookmark this article
Cardiovascular events, including thrombosis are a common complication in patients with myeloproliferative neoplasms (MPN) like polycythemia vera (PV) and essential thrombocythemia (ET).1 Approximately, 34-39% of patients with PV will develop an adverse cardiovascular event during the course of the disease, worsening their prognosis.1 Currently, the risk of thrombosis is stratified according to patient age (higher risk in > 60 years) and history of thrombotic events in patients with PV.2 For ET the driver Janus kinase 2 (JAK2) V617F mutation is also included in thrombotic risk stratification due to its association with an increased risk of thrombosis.2
Non-driver mutations in the DNA-methyltransferase 3A (DNMT3A), tet methylcytosine dioxygenase 2 (TET2), and the additional sex combs like 1 (ASXL1) genes, collectively known as DTA genes, have been associated with clonal hematopoiesis (CHIP) which increases the risk of developing coronary disease and myocardial infarction.1 Nevertheless, there is limited data on the role of DTA mutations in the prediction of thrombotic risk in patients with MPN. For this, Adrián Segura-Díaz and colleagues from the Hospital Universitario de Gran Canaria, Gran Canaria, ES, used next generation sequencing (NGS) to investigate whether pathogenic non-driver mutations can be used as predictors of thrombosis in MPN patients.1 The results of this study were published in Cancers and are summarized below.1
Initial MPN cohort
Case-control PV study
Initial MPN cohort
Case-control PV study
Table 1. Frequency of thrombotic events in patients with DTA and non-DTA mutated polycythemia vera1
DTA, DTA genes (DNMT3A, TET2, or ASXL1) |
||||
Thrombotic event |
n |
DTA mutated (%) |
No DTA mutation (%) |
p value (95% CI) |
---|---|---|---|---|
No |
30 |
34.5% |
76.9% |
0.0024 (2.02-22.32) |
Yes |
25 |
65.5% |
23.1% |
|
Total |
55 |
52.7% |
47.3% |
— |
This NGS study revealed that pathogenic mutations in DTA genes (DNMT3A, TET2, ASXL1) are significantly associated with the occurrence of thrombotic events in patients with PV. More specifically, the case control study suggested that TET2 mutations specifically are responsible for this association in patients with PV. The authors suggest that mutational analysis in DTA genes should be considered in current risk algorithms at diagnosis to identify patients with PV at higher risk of developing thrombosis.
Your opinion matters
Subscribe to get the best content related to MPN delivered to your inbox