Yoon-A Kang, PhD
Assistant Professor, Department of Medicine, Hematology Division
Washington University in St. Louis
Research project
Redirecting Myeloid Differentiation Trajectory to Treat Myeloproliferative Neoplasms
Summary
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.
Impact
Targeted therapies have revolutionized leukemia treatment, although they are not curative in most cases, as the cell population driving disease development and recurrence is usually not eradicated. Furthermore, many cancers are characterized by the accumulation of several mutations, and targeting only one specific mutation may not be the most efficient way to treat the disease. Additionally, there are still patients without known driver mutations, no targetable driver mutations, or that develop resistance to targeted therapies.
My project aims to find a treatment which is applicable to a broad range of myeloid malignancies independent of individual mutations using myeloproliferative neoplasms (MPNs) as a model system. I proposed to study NF-kB signaling, of which dysregulation are found in many human myeloid malignancies such as MPNs, secondary acute myeloid leukemia (sAML), and AML. In addition, MPNs exhibit a propensity to evolve to AML, and MPNs and myelodysplastic syndrome (MDS)/AML share many pathological characteristics such as increased cellular proliferation, highlighting that my study will have important implications for other hematologic malignancies including AML and MDS.
This study will also provide further insights into the early fate decision process underlying myeloid specification and help identify deregulated process of myeloid cell production that can be targeted to treat diverse blood cancers.
Therefore, the funding from LRF was crucial for me to embark on this exciting and impactful project and this funding set the cornerstone for my research program.
Leukemia Research Foundation grant
$100K awarded in 2022
Disease focus
Leukemia - myeloproliferative neoplasms (MPNs)
Research focus
Cancer cell biology (MPNs)