Grant: Doctoral: Vanier Canada Graduate Scholarships

In the last few years, researchers were surprised to find that we can detect mutated, pre-cancerous blood cells in >10% of people over the age of 65. These people have a ten-fold increased risk of developing leukemia, an aggressive blood cancer. Moreover, even after undergoing chemotherapy, these mutated pre-cancerous blood cells often persist in the patient, suggesting that they may be the source, or "root" of the new cancer when the patient relapses. We do not know how these roots develop, expand, or how to eradicate them. However, new data suggests that these roots alter or thrive in a certain kind of "soil": an inflammatory environment in the bone marrow and blood. Therefore, I hypothesize that the mutated pre-cancerous roots interact with the degree of inflammation in their environment, and this enables them to expand. To test this idea, I am using highly sensitive DNA sequencing to detect various pre-cancerous mutations in the blood of 400 otherwise healthy people over the age of 65 (recruited through Baycrest and Sunnybrook Hospitals). I am also quantifying markers of inflammation in these patients, and have found that certain mutations (e.g. in genes called "TET2" and "DNMT3A") are associated with more intense inflammation. I will also be testing how much these roots with certain gene mutations expand in mice. Interestingly, my preliminary analyses show that a specific inflammatory marker in the soil is more intense with these certain gene mutations, and I will test if blocking that intense signal causes the roots to regress. My work will enable earlier cancer surveillance for blood cancer development and its re-emergence. For Canada's aging population, this may facilitate a paradigm shift toward more targeted, preventative medicine. This means that aggressive, often unsuccessful cancer therapies could be avoided in an already frail population, which would improve individuals' quality of life and the healthcare burden overall.