Funding outcome

Leukemia is a cancer characterized by an uncontrolled growth/production of blood cells, and accounts for around 32% of all childhood cancers in Canada, earning it the title of most common childhood cancer across Canada. The utilization of anti-cancer drugs that act by killing and/or stopping the growth of cancer cells has found widespread success in the treatment of childhood leukemia. 6-mercaptopurine (6-MP) is one such drug that has been a staple in the treatment of childhood leukemia for decades. However, 6-MP is known to have unpredictable and damaging side effects that may be severe enough to cause one to stop treatment. One such negative side effect is toxicity within the liver, which can account for up to 44% of 6-MP unfavourable side effects. Another note of concern is that 6-MP must first enter cells via systems called 'transporters' to have anti-cancer effects. Our lab has identified the transporter called equilibrative nucleobase transporter 1 (ENBT1) as the main transporter 6-MP utilizes to enter cells. Interestingly, the liver is known to have high levels of ENBT1 transporters; however, the relationship between ENBT1 presence in the liver and 6-MP toxicity within the liver is currently not known. To investigate this relationship, our lab has genetically developed mice that have ENBT1 in their liver cells and those that do not; known as wildtype mice and knockout mice, respectively. We aim to extract liver cells from these wild-type & knockout mice to assess their ENBT1 levels as well as levels of 6-MP toxicity. By bettering our understanding of the relationship between ENBT1 levels and 6-MP toxicity within liver cells, we ultimately aspire to take the first steps in providing cancer doctors with the ability to better predict 6-MP liver toxicity and ensure childhood leukemia patients have the best possible treatment outcomes.