Visualising and targeting leukaemic stem cells in the bone marrow microenvironment

Chronic myeloid leukaemia (CML) is a cancer in the blood and develops following a specific mutation in a bone marrow-located blood stem cell. These CML stem cells represent a crucial target for treatment. We and others have shown that CML stem cells are not killed with currently available drugs and can become resistant leading to relapse of patients. Our previous work has also illustrated that autophagy (“self-eating”), a recycling process that maintains cell integrity, is an attractive target for CML stem cell eradication. This led to CHOICES, a phase II clinical trial, in which the combination of imatinib (first line therapy for CML patients) with the non-specific autophagy inhibitor hydroxychloroquine was tested in CML patients. However, unpublished results from the trial show that more specific autophagy inhibitors are required. The main aim of our Medical Research Scotland PhD project is to further understand how autophagy controls the way in which CML stem cells function and use the best laboratory models, including live imaging of bone marrow-located CML stem cells, to test novel pre-clinical drugs that block autophagy. We hope that results from this project will lead to development of novel therapy options for CML and other stem cell driven leukaemias.