Ann Mullally, M.D.
2018 Funding recipient
Biology and Therapeutic Targeting of Mutant SETBP1 in MDS
Discovery Research Grant 2018
Myelodysplastic syndrome (MDS) is a cancer arising in the bone marrow. In recent years, due to progress in gene sequencing studies we have been able to work out which genes are important for the development of MDS, which are associated with a worse prognosis and which drive progression to more aggressive diseases such as acute leukemia. We and others have found that a gene called SETBP1 is associated with a poor prognosis, at least in part because it seems to push MDS to become leukemia. Despite the fact that this gene seems to cause such bad outcomes we don’t understand well why this is and we currently have no way to inhibit SETBP1 as a treatment strategy. My project will focus on understanding how SETBP1 affects bone marrow cells in MDS and how it co-operates with other MDS-associated genes (e.g. SRSF2) to cause MDS to progress and become more difficult to treat. We will work out the other genes and proteins with which SETBP1 interacts with the goal of coming up with ideas to stop these interactions and block SETBP1 from causing MDS to progress. Through this work, we will come up with new and better ways to treat patients with MDS and improve their outcomes.