Exploiting Novel Therapeutic Vulnerabilities in Chronic Myelomonocytic Leukemia
Stephen Oh
PhD, MDWashington University in St. Louis
Project Term: November 1, 2023 - October 31, 2026
The overall objective of this project is to identify novel pathways that may be targeted for therapeutic benefit in CMML. We have identified abnormal inflammation mediated by RSK1 in CMML patient cells, and we hypothesize that RSK1 drives CMML disease development. We thus propose studies to determine how RSK1 contributes to CMML pathogenesis, and to evaluate the therapeutic potential of RSK1 inhibition for CMML patients.
Chronic myelomonocytic leukemia (CMML) is a chronic blood disorder that that can cause severe symptoms and early death. Currently available treatments have limited ability to modify the underling disease. We seek to better understand what drives CMML disease development and progression, so that we can develop better therapies for patients with these diseases. Our preliminary data indicates that the kinase RSK1 drives abnormal inflammation in CMML, and that targeting RSK1 may provide therapeutic benefit. We hypothesize that RSK1 contributes to CMML disease development. Therefore, we have proposed a combination of mouse and human studies to determine how RSK1 contributes to CMML pathogenesis, and to evaluate whether inhibition of RSK1 may have potential therapeutic benefits for CMML patients.