Leveraging dysregulated signaling networks for therapeutic benefit in myeloproliferative neoplasms
Stephen OhPhD, MD
Washington University in St. Louis
Project Term: October 1, 2021 - September 30, 2024
The objective of this project is to decipher mechanisms driving transformation of myeloproliferative neoplasms (MPNs) to secondary acute leukemia (sAML). We have identified increased expression of DUSP6 and RSK1 in sAML patient cells. Genetic/pharmacologic targeting suggest a role for DUSP6 and RSK1 in MPN development. We thus propose studies to determine how DUSP6 and RSK1 contribute to MPN pathogenesis, and to evaluate the therapeutic potential of DUSP6 and/or RSK1 inhibition for MPN patients.
Myeloproliferative neoplasms (MPNs) are chronic blood disorders that that can cause severe symptoms and early death. New treatments have become available that help ameliorate symptoms, but they do not reliably slow or halt disease progression. We seek to better understand what drives disease development and leukemic progression in MPNs, so that we can develop better therapies for patients with these diseases. Our preliminary data indicates that the phosphatase DUSP6 and the kinase RSK1 are abnormally expressed in MPNs. We hypothesize that DUSP6 and RSK1 contribute to the development and progression of MPNs. Therefore, we have proposed a combination of mouse and human studies to determine how DUSP6 and RSK1 contribute to MPN pathogenesis, and to evaluate whether inhibition of DUSP6 and/or RSK1 may have potential therapeutic benefits for MPN patients.