Grant: Doctoral Research Award: Canada Graduate Scholarships

Acute Myeloid Leukemia (AML) is a cancer of the blood and has one of the worst 5-year survival rates in Canada. The largest subtype of AML is called Cytogenetically Normal (CN) AMLs, with its most diagnosed mutation being to the nuclear trafficking protein Nucleophosmin1 (NPM1mut). NPM1mut CN-AMLs initially respond well to treatment, but more than half of patients will relapse. Our understanding of why patients relapse is limited, but emerging research has identified that the immune system plays a significant part. Our immune cells have an anti-cancer role in our bodies and can recognize and eliminate leukemic cells. However, this anti-cancer activity is often impaired in patients who experience relapse during treatment. Cancerous cells can circumvent the host immune system to avoid detection through a process called immune escape. The extent CN-AMLs utilize immune escape, and the regulatory mechanisms behind it, are largely unknown. Elucidating how immune escape may be activated provides us the opportunity to target leukemic cells and improve NPM1mut CN-AML patient survival rates. I have analyzed AML patient datasets and identified a novel subset of NPM1mut CN-AML patients whose leukemias exhibit properties strongly suggestive of immune escape. These patients have drastically reduced levels of Major Histocompatibility Complex (MHC), a molecule that is required for the immune system to initiate responses against cancerous cells. Furthermore, these patients have lower enrichment of immune cells in the bone marrow, at time of diagnosis. My research focuses on MHC loss as a mechanism of immune escape in CN-AMLs. I will perform experiments that test how MHC modulation affects immune activation and leukemic progression. Furthermore, I will assess how restoring MHC expression can impact immune cell function. My goal is to conduct translational research that can reverse immune escape in NPM1mut CN-AML and improve patient prognosis.