Yoon-A Kang, PhD

Myeloproliferative neoplasms (MPNs) are a group of diseases characterized by too many white blood cells, red blood cells, or platelets in the bone marrow. There are several well-known disease-causing mutations and researchers try to develop treatments targeting those mutations. However, in many cases, several mutations are accumulated to develop disease phenotypes. There are also patients without known driver mutations, no targetable driver mutations, or that develop resistance to targeted therapies. Therefore, a better understanding of the mechanisms underlying myeloid cell expansion, a shared feature of various MPNs, could help develop new treatments to be used in combination with current targeted therapies or as alternatives for patients not eligible for current therapies. My study aims to find a treatment, which is applicable to a broad range of MPNs independent of individual mutations. My previous work found that there is a specific immature bone marrow population, which is expanded in various MPN mouse models regardless of their driver mutations. In this study, I propose to study NF-kB signaling and GATA-2, two commonly dysregulated pathways in human myeloid malignancies, to control the production of distinct subsets of the expanded immature bone marrow population. My study will provide insights into the common mechanism underlying MPN development, and clues to develop broadly applicable therapeutic interventions.