Discovery of Mechanisms Driving Evolution of Clonal Hematopoiesis to Bone Marrow Failure from Dnmt3a-Mutant Stem Cells
EvansMDS Discovery Research Grant 2018
Aging is a major risk factor for developing myelodysplastic syndrome (MDS). We currently do not have reliable clinical tests to determine which individuals in our population are at greatest risk of developing MDS. We also do not have any therapies that can prevent MDS from occurring in these individuals. The proposed project will use a new mouse model of aging associated MDS that we have created to determine why MDS develops from aged stem cells. We will study whether specific changes (mutations) in the DNA of aged normal stem cells cause MDS. We will also study whether specific changes that occur with aging in the environment where stem cells live (the bone marrow) cause MDS. The information gained in this study can be used to develop new methods for screening individuals, as they age, to determine their risk of MDS development. Furthermore, this information can also be used to engineer new therapies for prevention of MDS development or relapse.