“Assessing clonal fitness and mechanisms of clonal evolution in RUNX1-FPD.”

Dr. Xiao has developed a project that aims to understand how a germline RUNX1 mutation cooperates with secondary, somatic mutations to drive the initiation and progression of leukemia. He will use novel mouse models he generated in Dr. Ross Levine’s laboratory that uniquely enable the sequential activation of somatic mutations in common leukemia-associated genes like TET2 and FLT3 in a mouse with a germline Runx1 mutation that can be reversed to a wild type state.

This ability to reverse the status of the Runx1 allele from a pathogenic mutated allele to a wild type, functional allele will allow Dr. Xiao to determine what role a pathogenic Runx1 mutation has in the process of leukemia initiation, progression and maintenance. His research will provide insights into the underlying mechanisms that control clonal fitness and leukemic transformation in RUNX1-FPD.

Such insights may help us identify which RUNX1-FPD patients are at the highest risk of leukemia and inform the development of novel therapeutic approaches to prevent/intercept leukemic initiation.