Grant: Operating Grant: Epigenetics Clinical Translation

In 2013, according to the Canadian Cancer Society, 1315 patients in Canada were diagnosed with the blood cancer acute myeloid leukemia (AML) and 1047 died of the disease. AML is the most common adult blood cancer and one of the most deadly forms of cancer. Unfortunately, these numbers have not changed much in the last 30 plus years. This is due primarily because only minor changes to therapy have occurred over this time period. About 40 year ago, an innovative chemotherapy known as induction therapy was introduced as the frontline treatment for AML patients. While some modest improvements have been made to induction therapy, new innovative therapeutic approaches are necessary to make substantive improvements to the survival of AML patients. In contrast to the "one size fits all" induction therapy, we propose to implement a "precision medicine" strategy to treat AML patients. To implement precision medicine in AML, we need to identify different sub-classes of AML, identify which patients fit a particular subclass, develop targeted therapies for these sub-classes of AML and treat the patients accordingly. In this proposal, we will focus on the "epigenetic state" of AML because these states can be reversed. Recently, we demonstrated in mice that we can reverse the epigenetic state of a group of AML patients who are resistant to induction therapy. This group of patients are known as "refractory" AML patients. In this proposal, we aim to determine how different drugs reverse the epigenetic state of this group of refractory AML patients and perform additional experiments to enable us to file for a precision medicine clinical trial in this group of AML patients. We will also develop the tools to treat other groups of refractory and relapse AML patients. These tools include methods to identify these patients at diagnosis and novel drugs to treat these normally drug resistant AML cells.