Timothy Barrow, PhD

Chronic lymphocytic leukemia (CLL) is the most common adult form of leukemia. While traditionally considered incurable, new drugs are coming into the clinic that offer hope of extended remission or even cure. In order to monitor how patients respond to treatment and predict risk of relapse, we need sensitive laboratory assays that measure the number of leukemic cells that remain in the blood, referred to as minimal residual disease (MRD). Genetic assays that detect abnormalities in DNA are routinely used for other forms of leukemia but have not been developed for CLL because suitable targets have not been found. I have identified changes in the chemical modification of DNA, referred to as DNA methylation, that are present in more than 90% of CLL patients. To determine whether these could be used for measuring MRD, I will address two questions. Firstly, I will determine whether the loss of DNA methylation is caused by mutations that prevent the DNA from being methylated. This is important because detecting mutations is simpler and cheaper to do. Secondly, I will determine whether these changes are only present in leukemic cells in the patient’s blood, as early genetic changes leading to cancer can sometimes be seen in normal cells as well. This project will determine whether the changes I identified in CLL patients can be used to develop new assays for measuring MRD, which would benefit patients by improving the monitoring of their response to treatment and risk of relapse.