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Identifying neutrophilic granulocytes as key contributors and therapeutic targets in the development and progression of BCR::ABL1 negative myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders and form a distinct group of hematologic malignancies. MPNs are classified as BCR::ABL1 positive or negative, respectively indicating the presence/absence of a reciprocal translocation between chromosome 9 and 22. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) form the 3 most frequent BCR::ABL1 negative MPN and tend to show unique patterns of cytokine expression within bone marrow and peripheral blood. Common adverse events of MPN are arterial and venous thrombosis, pruritus, hyperviscosity-syndrome and hepatosplenomegaly due to extramedullary hematopoiesis. The 5-year mortality is approximately 19%, 19.2% and 51% for PV, ET and PMF respectively.  Additionally, 10% of all patients will develop secondary acute myeloid leukemia (sAML) which is more aggressive compared to “classic” AML and has a median survival of approximately 2.4 months. Current treatment strategies in MPN are unable to hinder disease progression or transformation.

Recent research indicates MPNs represent a biological continuum in which all entities can evolve into each other. Until now the exact mechanisms of disease development and transformation are unknown. Various observations support a potential role of neutrophilic granulocytes, the most abundant type of white blood cells, in the development of MPN. As such increased neutrophilic leukocytosis is associated with worse prognosis and a higher risk for thrombosis.

This research project will explore the contributing role of neutrophilic granulocytes in the development and progression of MPNs and will hopefully result in the identification of new therapeutic targets.

Date:4 Oct 2023 →  Today
Keywords:myeloproliferative disorders, neutrophils
Disciplines:Inflammation, Innate immunity, Hematology
Project type:PhD project