TY - JOUR

T1 - Interferon alpha-2 treatment reduces circulating neutrophil extracellular trap levels in myeloproliferative neoplasms

AU - Massarenti, Laura

AU - Knudsen, Trine Alma

AU - Enevold, Christian

AU - Skov, Vibe

AU - Kjær, Lasse

AU - Larsen, Morten K.

AU - Larsen, Thomas S.

AU - Hansen, Dennis L.

AU - Hasselbalch, Hans C.

AU - Nielsen, Claus H.

N1 - 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.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - interferon alpha (IFN-α)

KW - JAK2V617F

KW - myeloproliferative neoplasm (MPN)

KW - neutrophil extracellular traps (NETs)

KW - thrombosis

U2 - 10.1111/bjh.18845

DO - 10.1111/bjh.18845

M3 - Journal article

C2 - 37211985

AN - SCOPUS:85159833004

VL - 202

SP - 318

EP - 327

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 2

ER -