Single Cell Signaling Profiles In High-Risk Pediatric Leukemia

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children.  Although great strides have been made in improving outcomes for children with ALL, some groups of children will not survive this disease.  Recent discoveries have found that genetic mutations in proteins that are involved in normal lymphocyte development play a role in the development of leukemia, including a protein called Ikaros. The mechanism by which Ikaros causes leukemia is unknown.  Our laboratory has developed techniques to investigate cell-signaling networks that are informative in understanding disease mechanism and can be examined on the single cell level.  These signaling networks have been predictive of disease outcome in previous studies with lymphoma and leukemia.  The overall goal of this project is to examine cell-signaling networks in bone marrow samples from children with high-risk leukemia in order to understand how mutated Ikaros causes leukemia in children.  We suspect that by examining these signaling networks, we will find that dysfunctional Ikaros protein provides leukemia cells alternative pathways to survival or proliferation.  This knowledge will improve our understanding of the role of Ikaros in causing leukemia and reveal new targets for therapy.