Grant: Project Grant

In 2016, approximately 22,510 Canadians were living with leukemia and an estimated 2,900 Canadians died from leukemia. In Canada, the five-year survival rate for leukemia remains poor at 58% for males and 59% for females. Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults. Despite exciting advances in our understanding of AML and the availability of more aggressive treatment regimens, ~30% of treated patients eventually relapse and suffer from very poor overall survival. Therefore, additional approaches to understanding how these diseases develop and become therapy resistant is badly needed. While genetic mutations in AML have been identified and well characterized, much less is known about how changes in the processes regulating protein synthesis contribute to the pathogenesis of AML. Our objective is to reveal the roles of these fundamental mechanisms in leukemia transformation, progression and resistance to therapy. Our work has identified a candidate regulator of this critical process in AML. In this project, we will perform functional genomics using human and mouse models to further functionally characterize these novel targets in AML. We will employ a broad range of molecular biology techniques and a global approach using state-of-the-art next generation sequencing techniques to decipher mechanisms of mRNA biogenesis and translation while exploring avenues for therapeutic interventions. The work will identify potential therapeutic targets and provide the scientific foundation for future developments of therapy targeting these pathways to improve outcomes in AML patients.