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

• Published in: British journal of haematology 2023-07, Vol.202 (2), p.318-327
• Main Authors: Massarenti, Laura, Knudsen, Trine Alma, Enevold, Christian, Skov, Vibe, Kjær, Lasse, Larsen, Morten K., Larsen, Thomas S., Hansen, Dennis L., Hasselbalch, Hans C., Nielsen, Claus H.
• Format: Article
• Language: English
• Subjects: Alleles; Extracellular Traps; Hematology; Humans; Hydroxyurea; Hydroxyurea - therapeutic use; interferon alpha (IFN‐α); Interferon alpha-2; JAK2V617F; Janus Kinase 2 - genetics; Leukocytes (neutrophilic); Lymphocytes; Mutation; Myeloproliferative Disorders - drug therapy; Myeloproliferative Disorders - genetics; myeloproliferative neoplasm (MPN); Neoplasms; neutrophil extracellular traps (NETs); Neutrophils; Thrombosis; Tumors; α-Interferon
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.18845

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