Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of blood cells. T-ALL represents 15% of pediatric, and 25% of adult cases of acute lymphoblastic leukemia. Current therapy with high intensity combination chemotherapies achieve 5-year survival rates of approximately 90% and 50% for pediatric and adult T-ALL, respectively. However, these therapies have a broad specificity of cellular targets, and as such, are associated with life-long cytotoxic effects. The consequences of chemotherapy can be drastic, particularly in the pediatric setting, highlighting the importance for development of targeted therapies. In order to improve patient treatment outcome and to minimize the cytotoxic side-effects associated with chemotherapy, dedicated efforts are required to identify and validate candidate therapeutic targets. High-throughput methods are needed to enable screening large classes of genes for their therapeutic potential. Furthermore, reliable models that can faithfully recapitulate the disease state are required to accurately understand disease mechanisms. Recently, our lab developed the first ever model of human T-ALL derived from normal blood cells. This model provides us with an accurate representation of human disease, allowing us to understand the pathways that lead to pathogenesis. To identify novel therapeutic targets, we propose to use our model of human T-ALL to perform high-throughput screening methodologies that assess the importance of 300 epigenetic factors in disease maintenance. Importantly, our findings may provide an avenue for targeted therapy in T-ALL.