Targeting Pleckstrin-2 for the treatment of myeloproliferative neoplasms (19POST34381031)

Myeloproliferative neoplasms (MPNs) are a group of bone marrow diseases with excessive production of blood cells. Patients with MPNs show significantly increased risk of developing thrombosis that often leads to morbidity and mortality. Current therapies on MPNs are not curative. In addition, patients often encounter drug resistance and significant side effects. More recent findings further reveal increased chance of B-cell lymphoma in patients treated with JAK2 inhibitors. Therefore, new therapeutic strategies are urgently needed. Our proposed study focuses on a novel target that plays an important role in the pathogenesis of MPNs. We propose to identify small molecule inhibitors of this novel target using high-throughput screenings, established bioassays, and animal models. Successful completion of this project will lay the foundation for clinical trials of these novel inhibitors as single agents or in combination with other compounds to treat patients with MPNs, especially those with thrombosis.