Metabolic Syndrome and Risk of Chronic Philadelphia Negative Myeloproliferative Neoplasms

Chronic Myeloproliferative neoplasms (MPNs), such as polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are defined by clonal myeloid proliferation . Thrombotic events are the leading cause of morbidity and mortality in these patients . Traditional cardiovascular risk factors (CVRFs) critically exacerbate disease severity, accelerate progression to overt myelofibrosis, and significantly reduce overall survival .

Metabolic syndrome components overlap substantially with MPNs; in PV, hypertension affects 39-70%, dyslipidemia 15-38%, diabetes 7-16%, and obesity 7.5% . Epidemiological evidence demonstrates that these factors are independent predictors of arterial and venous thrombosis . while obesity is significantly linked to ET and exacerbates total symptom burden .

The mechanistic link between Metabolic syndrome and MPNs involves the JAK2V617F mutation, which induces constitutive JAK/STAT signaling and alters both lipid and glucose metabolism . MPN clones exhibit a high dependence on glucose, marked by upregulated glycolysis, elevated oxidative phosphorylation, and increased PFKFB3 expression . This metabolic reprogramming, combined with chronic systemic inflammation, cytokine overproduction, and oxidative stress, promotes severe endothelial dysfunction, accelerated atherogenesis, and hypercoagulability .

Current literature assessing different components of Metabolic syndrome in MPNs is limited by methodological gaps, often relying on retrospective data lacking comprehensive baseline metabolic parameters . Therefore, rigorous case-control designs with robust statistical extraction are required. Utilizing standard statistical software environments to perform multivariate adjustments is crucial to properly control for disease heterogeneity.