This proposal focuses on a subtype of pediatric leukemia called AMKL in which the megakaryocytes, cells necessary for blood clotting, become cancerous.
This leukemia is caused by a recurrent mismatch in the genetic material leading to expression of a cancer-specific protein called RBM15-MKL1 (RM).
I propose to study how this leukemia forms using a new mouse model in which I can induce expression of RM. Since this leukemia occurs in newborns and may thus start in utero, I propose to use the mouse model to evaluate how the leukemia starts prior to birth.
Furthermore, I will determine what additional genetic changes need to cooperate with RM to promote leukemia. Completion of this work will lead to a deeper understanding of how leukemia is initiated and will open new avenues of research into targeted treatments.
