Grant: Operating Grant

Acute Myeloid Leukemia (AML) is one of the deadliest types of cancers. Thirty to forty percent of AML patients younger than 60 years of age are long-term survivors, while only 10-15% of patients over 60 years of age are long-term survivors. The standard treatment has not changed in over 30 years, which is why survival rates have not improved during this period. The exception to this dismal news is that some targeted therapies have been developed to specific molecular causes of AML. Patients with these types of AML have responded well to drugs that are specific to these mutations. Unfortunately, in about half of the AML patients, mutations associated with their AML have not been identified. We have recently identified a protein called PCL2 that regulates the expression of many other proteins, including many that are involved in cancer. PCL2 expression is lost in 40% of AML patients. Our preliminary data suggest that PCL2 is important in controlling cell growth and inducing mutated cells to die, processes that prevent cancer development. Thus, we believe that PCL2 could be a target for new chemotherapeutic drugs to treat patients in a targeted manner. However, to pursue this strategy, we need to understand the function of PCL2 in normal blood stem cells and AML cells. In this study, we will analyze the function of PCL2. We will turn off the expression of PCL2 in both normal blood stem cells and AML cells. We will determine how the loss of expression of PCL2/PRC2 proteins changes the molecular networks that regulate cell behaviour including growth and death of blood stem cells and AML cells. Knowing the function of PCL2 may help us to induce AML cells to die.