Advanced Clinician Scientist-Programm 2026

Thema: "Role of epigenetic regulation in the pathogenesis of thrombosis and disease phenotype in BCR::ABL1-negative myeloproliferative neoplasms (MPN)"

Zusammenfassung:
BCR::ABL1-negative myeloproliferative neoplasms (MPN) are associated with a persistently high risk of arterial and venous thrombosis despite modern therapy. Particularly, splanchnic vein thrombosis is a life-threatening complication and often requires liver transplantation. The molecular mechanisms underlying these complications remain insufficiently understood. Emerging evidence suggests that epigenetic mutations such as DNMT3A, TET2, and ASXL1, known as CHIP, may contribute to thrombotic risk. However, the mechanistic basis remains unclear. The proposed project investigates endothelial involvement to explore the contribution of JAK2-V617F allele frequency and somatic non-driver mutations to thrombotic events in the splanchnic region. Furthermore, the order of acquisition of driver and non-driver mutations will be determined by colony genotyping. The long-term goal is the development of a molecularly integrated thrombosis risk score incorporating non-driver mutations to improve stratification and prevention of thrombosis in MPN patients.