Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer.  In 5% of cases, the malignant cells in this condition contain a chromosomal abnormality that leads to the production of an abnormal protein called E2A-PBX1. E2A-PBX1 plays an important role in transforming normal blood-forming cells into leukemia cells.  My co-workers and I are seeking to better understand the molecular mechanisms by which E2A-PBX1 causes leukemia.  In order to do this, we require an experimental system that detects the ability of E2A-PBX1 to turn normal lymphocyte-forming cells into leukemia cells, as actually happens in patients with leukemia.  Since no such system exists currently, this project aims to develop one.  This system will allow us to determine, for example, which of the hypothetical mechanisms of E2A-PBX1 cancer causation currently being investigated in various labs are actually relevant to patients with leukemia.  It will also help us understand how E2A-PBX1 collaborates with other leukemia-inducing alterations to transform normal lymphocyte precursor cells into leukemia cells.