Philadelphia-Negative Myeloproliferative Neoplasms: Diagnostic Insights, Genetic Factors and Vascular Impact on Survival

Abstract

The thesis addresses Philadelphia-negative myeloproliferative neoplasms (MPNs), a group of clonal hematopoietic stem cell disorders encompassing polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis (MF) and MPN Unclassifiable (MPN-U). These diseases, characterized by somatic mutations in JAK2, CALR, and MPL, involve diagnostic challenges, variable risk of vascular complications, and diverse survival outcome. The studies presented in this dissertation aim to enhance the understanding of genetic predisposition to treatment outcome, survival, and vascular complications associated with MPNs. The first study examines genetic variations in IL28B (IFNL3) and their influence on interferon- alpha therapy outcomes, demonstrating the potential for genetic markers to predict treatment efficacy. The second and third studies, based on data from the Swedish MPN registry, investigate survival patterns and vascular complications in patients with PV, ET and MF. These finding emphasize the prognostic significance of vascular events and the protective role of cytoreductive therapies. The fourth study evaluates the heterogeneity of patients with MPN-U, addressing diagnostic challenges and their implications for classification and clinical management while documenting survival patterns and the incidence of thrombotic complications. Together, these studies enhance the understanding of MPNs by addressing diagnostic challenges and examining clinical and therapeutic outcomes. The findings underscore the need for tailored approaches in diagnosis, risk stratification, and treatment to improve patient care and provide a foundation for further research into these complex disorders.