Abstract

Background: Myeloproliferative neoplasms (MPNs) are shaped by both oncogenic mutations and chronic inflammation. Nuclear Factor-kappa B (NF-κB) is a central regulator of inflammation, yet its role in defining the clinical profile of Middle Eastern its relationship to molecular drivers and clinical outcomes in an Iraqi MPN cohort. Methods: We conducted a combined prospective and retrospective analysis of 110 patients with BCR-ABL1-negative MPNs (40 PV, 40 ET, 30 PMF) alongside 40 age- and sex-matched healthy controls. Peripheral blood was tested for JAK2, CALR, and MPL mutation ns using real-time PCR. NF-κB/p65 mRNA expression was quantified by RT-qPCR. Results: Median age at diagnosis (55-58 years) was younger than Western cohorts, consistent with regional trends. JAK2 (V617F) was the most frequent mutation (61.8%). NF-κB/p65 expression was significantly elevated across all MPN subtypes compared with controls (p < 0.001), following a severity gradient: PMF (3.6-fold) > PV (2.7-fold) > ET (2.2-fold). The highest level of activation was observed in JAK2 mutation cases (3.2-fold increased), but elevated NF-κB levels were also observed in CALR/MPL cases (2.4-fold increased) and patients with triple-negative results (2.6-fold increased). Clinically, elevated NF-κB levels were closely associated with splenomegaly (p < 0.01) and thrombosis (p < 0.001). Conclusions: The transcription factor NF-κB/p65 links malignant proliferation and inflammation in bone marrow proliferative diseases, with its activation accurately reflecting disease severity and vascular risk. Therefore, it can be considered a biomarker and therapeutic target for such diseases.