Robert Bowman, PhD

Adult acute myeloid leukemia (AML) is characterized by expansion of rapidly dividing stem cells in the bone marrow. This disease can be caused by the accumulation of mutations in genes known to control stem cell growth rate. The most mutated gene in AML is FLT3, a mutation which is associated with both poor prognosis and response to chemotherapy. Therapeutic intervention with FLT3 inhibitors has been shown to extend overall survival, however most patients relapse with disease. We hypothesize that relapse is driven in part by the inability of FLT3-inhibitors to completely eradicate drug persistent leukemic stem cells. Our approach takes advantage of recently developed preclinical models of AML which accurately reflect the timing of AML development as seen in patients. With these models we aim to understand how cells can survive following FLT3 inhibition and to test novel therapeutic strategies that not only inhibit FLT3 activity, but completely degrade FLT3 protein. The overall impact of this work will be to identify new cell signaling pathways that can be inhibited to improve FLT3-targeted therapy, and to credential FLT3-protein degradation as a therapeutic strategy in AML.