Protein disulfide isomerase in Philadelphia-negative myeloproliferative neoplasms: a case–control study
Background
Classic Philadelphia-negative myeloproliferative neoplasms (MPNs), such as polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), are defined by the unregulated production of bone marrow components resulting from the clonal expansion of multipotent bone marrow progenitors. Thrombotic complications represent a major cause of morbidity and mortality in BCR-ABL-negative MPNs. Multiple factors have been identified as potential contributors to thromboembolism in MPN patients, yet the exact pathophysiology remains poorly understood. Also, the current risk stratification systems lack early predictors of thromboembolic risk, mandating the need to identify new surrogate thrombotic markers. Despite the use of cytoreductive therapy and antithrombotic drugs, unfortunately, the incidence rate of thrombosis remains high, which advocates for further research to discover novel antithrombotic therapeutic targets. Protein disulfide isomerase (PDI), an endoplasmic reticulum protein that is critical for protein folding, is released by stimulated platelets and endothelial cells and was found to play a regulatory role in thrombosis. Inhibitors of PDI have been shown to prevent thromboembolic events in cancer patients. We aimed to study the PDI level in MPN patients and assess its role as a marker of increased thromboembolic risk in MPN patients, which might shed light on a new area of investigation in the prognosis and prevention of thromboembolism in MPN patients.
Methods
This is a case–control study where we investigated the serum level of PDI in a cohort of MPN patients in comparison to a control group. Serum PDI level was measured using ELISA to assess if PDI level is pathologically elevated in MPN patients; we also correlated the PDI level with either history/recent thrombotic events or the presence of silent thrombosis screened for by venous and arterial duplex.
Results
PDI levels were found to be pathologically elevated in MPN patients when compared to the control group. As a secondary outcome, we aimed to correlate the level of PDI to different clinical and imaging parameters, but no significant association could be found.
Conclusion
PDI may have a possible role in the underlying pathogenesis of thrombotic events in Philadelphia-negative MPN patients and may have a role in predicting a higher risk of developing thromboembolic events, and this may shed light on the possible future use of PDI as a therapeutic target for prevention of thrombosis in MPN patients.
