Interferon alpha-2 treatment reduces circulating neutrophil extracellular trap levels in myeloproliferative neoplasms
Research output: Contribution to journal › Journal article › Research › peer-review
Neutrophil extracellular traps (NETs) may play a pathogenic role in the thrombosis associated with myeloproliferative neoplasms (MPNs). We measured serum NET levels in 128 pretreatment samples from patients with MPNs and in 85 samples taken after 12 months of treatment with interferon alpha-2 (PEG-IFNα-2) formulations or hydroxyurea (HU). No differences in NET levels were observed across subdiagnoses or phenotypic driver mutations. In PV, a JAK2V617F+ allele burden ≥50% associated with increased NET levels (p = 0.006). Baseline NET levels correlated with neutrophil count (r = 0.29, p = 0.001), neutrophil-to-lymphocyte ratio (r = 0.26, p = 0.004) and JAK2V617F allele burden (r = 0.22, p = 0.03), particularly in patients with PV and with allele burden ≥50% (r = 0.50, p = 0.01, r = 0.56, p = 0.002 and r = 0.45, p = 0.03 respectively). In PV, after 12 months of treatment, NET levels decreased on average by 60% in patients with allele burden ≥50%, compared to only 36% in patients with an allele burden <50%. Overall, treatment with PEG-IFNα-2a or PEG-IFNα-2b reduced NETs levels in 77% and 73% of patients, respectively, versus only 53% of HU-treated patients (average decrease across treatments: 48%). Normalization of blood counts did not per se account for these reductions. In conclusion, baseline NET levels correlated with neutrophil count, NLR and JAK2V617F allele burden, and IFNα was more effective at reducing prothrombotic NET levels than HU.
| Original language | English |
|---|---|
| Journal | British Journal of Haematology |
| Volume | 202 |
| Issue number | 2 |
| Pages (from-to) | 318-327 |
| Number of pages | 10 |
| ISSN | 0007-1048 |
| DOIs | |
| Publication status | Published - 2023 |
Bibliographical note
Funding Information:
The authors thank all the participating patients and their families, all investigators, research coordinators and site staff in Denmark. This study was supported by grants from OUH Frie Forskningsmidler, OUH‐Region Sjaelland Faelles Forskningspulje, Region Hovedstadens Forskningsfond til Sundhedsforskning, Fonden til Lægevidenskabens Fremme, Ellen og Aage Fausboells Helsefond af 1975, Swedish Orphan Biovitrum, Region Sjaellands Sundhedsvidenskabelige Forskningsfond (Ordinaer), Region Sjællands Sundhedsvidenskabelige Forskningsfond (RSSF) 2018 and Gangstedfonden. The sponsors of this study are non‐profit organizations that support science in general. They had no role in gathering, analysing or interpreting the data.
Funding Information:
H.C.H has received a research grant from Novartis A/S and is in the Advisory Board for AOP Orphan. The other authors declare no competing financial interests.
Funding Information:
The authors thank all the participating patients and their families, all investigators, research coordinators and site staff in Denmark. This study was supported by grants from OUH Frie Forskningsmidler, OUH-Region Sjaelland Faelles Forskningspulje, Region Hovedstadens Forskningsfond til Sundhedsforskning, Fonden til Lægevidenskabens Fremme, Ellen og Aage Fausboells Helsefond af 1975, Swedish Orphan Biovitrum, Region Sjaellands Sundhedsvidenskabelige Forskningsfond (Ordinaer), Region Sjællands Sundhedsvidenskabelige Forskningsfond (RSSF) 2018 and Gangstedfonden. The sponsors of this study are non-profit organizations that support science in general. They had no role in gathering, analysing or interpreting the data.
Publisher Copyright:
© 2023 British Society for Haematology and John Wiley & Sons Ltd.
- interferon alpha (IFN-α), JAK2V617F, myeloproliferative neoplasm (MPN), neutrophil extracellular traps (NETs), thrombosis
Research areas
ID: 362692106