Identification, characterisation and therapeutic targeting of leukaemic stem/propagating cells in Acute Myeloid Leukaemia

Every year, around 3,000 people in the UK are diagnosed with Acute Myeloid Leukaemia (AML), the most common aggressive leukaemia, and for patients over 60 the cure rate is just 5%. This matters because current treatments fail most patients. Even among those under 60, half still die from the disease. The core problem is that doctors do not fully understand which genetic changes in a patient’s DNA turn normal blood stem cells into cancerous leukaemic stem cells that resist therapy and cause relapse. This project will map the complete set of DNA mutations in both AML and its pre-leukaemic condition, Myelodysplasia (MDS), and work out exactly how those changes hijack blood stem cells. If the researchers succeed, they will identify the specific genetic weaknesses of leukaemic stem cells that could be targeted with new drugs. This would provide a rational basis for designing therapies that kill the root of the disease rather than just the bulk of leukaemia cells, potentially improving survival rates for the majority of AML patients who are over 60. The work also serves as a model for understanding fundamental principles of how cancers arise and evolve, which could inform treatment strategies for other malignancies.