Project 466934

Acute Myeloid Leukemia (AML) is a common, aggressive type of leukemia. The progression of AML depends on the function of cells called leukemic stem cells (LSCs). Research shows that AML patients with high LSC content have an aggressive form of AML and have lower survival rates than patients with low LSC content. As such, it is necessary to investigate therapies that target LSCs to improve AML patient outcomes. Recent studies in our research group identified that AML patients with very aggressive disease and poor health outcomes have high levels of a protein called INPP4B. INPP4B is also reported to play a role in lysosomal function and activity. Additionally, previous research shows that lysosomal function is important to LSCs function. However, there is limited research linking LSCs, INPP4B overexpression, and lysosomal function to AML prognosis. This study aims to identify the role of INPP4B overexpression in lysosomal function and LSC content in AML. It is hypothesized that INPP4B overexpression plays a critical function in LSCs and promotes AML progression by altering lysosomal function. This study examines signalling alterations, lysosomal functions, and AML progression using mouse models of leukemia. Additionally, lysosomal inhibitors will be introduced to measure their role in AML progression. This research is significant as it aims to identify molecular pathways impacted by INPP4B in the hopes of generating new AML therapies that block INPP4B function and eliminate LSCs.