Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

In 2017, there was an average of 17 patients diagnosed with leukemia (blood cancer) every day in Canada. The National Cancer Institute (US) calculated an overall 5-year survival rate of 56% for various blood cancers. This is because most current therapies are short-lived; drug resistance and relapse pose significant clinical problems. Chronic myeloid leukemia (CML) can be treated with the Imatinib Mesylate (IM) drug; however, this is not a widespread cure. Life-long treatment is required, with potential long-term side-effects and a high cost. At first, CML cells respond well to the drug, but the treatment loses its effect over a short period. Our lab and others have discovered that this is due to the drug's inability to kill the blood cancer stem cells, which can replenish the pool of blood cancer cells. Therefore, new therapies targeting other critical cancer-causing genes are required to eliminate blood cancer stem cells. IM is used to stop the activity of an unusually active fusion protein in CML called BCR-ABL. Prolonged IM treatment eventually leads to drug resistance and we must find alternative treatment strategies to overcome drug resistance. AHI-1, a key cancer-causing protein that interacts and enhances the effects of BCR-ABL could be a potential target. AHI-1 is abnormally expressed in blood cancer stem cells and is a major player in abnormal blood cancer stem cell activities and resistance in IM treatment. Another protein, Dynamin-2 (DNM2), also contributes to the characteristics of CML. BCR-ABL in the presence of AHI-1 can better activate DNM2 to give blood cancer cells a growth advantage. Experiments will be performed to understand the effects of the interaction between these proteins to uncover a potential therapeutic strategy to overcome drug resistance. Studying the interactions and its effect can help better understand how to overcome the consequences of the interaction, thus improving the success rate of treating drug-resistant leukemia patients.