Grant: CIHR Fellowship

The early T-cell progenitor acute lymphoblastic leukemia (ETP-ALL) is an aggressive blood cancer resulting from the malignant transformation of white blood cells (the type T leukocytes). Current treatments that are based on intensive chemotherapy are not always efficient, and are often coupled with debilitating toxicities and early relapse. Furthermore, once ETP-ALL patients have relapsed, very few options are available to them. Therefore, there is an urgent need to develop new therapies that are more efficient and less toxic. It was recently discovered that a specific protein named MEF2C is responsible for the malignant transformation of healthy blood cells, leading to the development and maintenance of ETP-ALL leukemia. These findings are highly promising as they suggest that by targeting this protein, we may be able to develop new therapies that are more efficient and less toxic. However, prior to being able to develop new therapies, we must understand precisely at the molecular level how this protein is working in leukemia, such that we can identify new drugs that will be efficient in inhibiting its function. Therefore, in this project, we will first characterize the molecular function of MEF2C in leukemia. Precisely, we will use advanced methods of protein analysis to identify other proteins that work with MEF2C, and we will then identify all the genes in leukemic cells that are regulated by MEF2C. The results from these experiments will allow us to identify novel molecular targets in leukemic cells that can be inhibited by specific drugs. In a second step, we will use these newly identified drugs to eliminate leukemic cells in animal models of leukemia. We will select specific drugs that are able to efficiently eradicate leukemic cells while preserving the healthy surrounding tissues. Results from the proposed experiments will allow us to propose new therapeutic approaches for patients with ETP-ALL based on "a targeted therapy treatment".