Some patients with myeloproliferative neoplasms (MPNs) show a high risk of complications related to thromboembolisms, which may be associated with cell death related to a process called neutrophil extracellular trap formation (NETosis). A study found that relationships between NETosis and thrombosis in patients with MPNs appear to be complex. Results were reported in the journal Blood Advances.
“NETosis has been observed in a large variety of diseases and has also been linked to thrombosis formation,” the researchers wrote in their report. Neutrophil extracellular traps appear to aid in thrombosis formation through a variety of characteristics, ranging from providing a scaffold for thrombus development to binding and activation of related factors.
Using peripheral whole blood and serum samples taken from patients with MPNs and healthy donors, the researchers evaluated the effects on clinical end points when NETosis is induced in vitro. NETosis induction in samples was enabled by ionomycin. Results of this induction were evaluated by nucleosome-release assays visualized through an enzyme-linked immunosorbent assay, in addition to fluorescence-based detection of free DNA. The population of patients with MPNs included both treated and untreated patients.
There were 103 patients with MPNs evaluated in this study and 28 healthy donor individuals. Overall, quantification of released nucleosomes in samples from patients with MPNs suggested that MPNs were linked to a greater susceptibility to NETosis than seen with healthy donor samples. This difference was statistically significant across the overall population (P =.0063), but it reportedly showed variable significance across MPN subtypes, potentially owing to small sample sizes for some subtypes.
The NETosis rate was found to be associated with mutational status. Mutations that were associated with NETosis included JAK2 V617F, mutations targeting JAK2 exon 12, and CALR mutations. JAK2 allelic burden, however, was not linked to a significantly greater rate of NETosis. The researchers noted that rarer mutations may also be associated with NETosis, but that the sample sizes involving rarer mutations were relatively small.
NETosis did not show a significant link to thrombosis history or to multiple laboratory parameters. However, patients with MPNs who were untreated appeared to show the lowest rates of NETosis.
“This observation of low NETosis background levels in patients with low levels of disease activity may support the role of NETosis as a facilitator of thrombogenesis,” the researchers wrote in their report. “The individual thrombotic event, however, is probably triggered by additional still partially unknown factors,” they concluded.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Schmidt S, Daniliants D, Hiller E, Gunsilius E, Wolf D, Feistritzer C. Increased levels of NETosis in myeloproliferative neoplasms are not linked to thrombotic events. Blood Adv. 2021;5(18):3515-3527. doi:10.1182/bloodadvances.2020004061