Acute myeloid leukaemia (AML) is a blood cancer that is becoming more common as the population ages. Although treatment has improved in recent years, relapse remains common and is often fatal. One strategy to attack these leukaemia cells is to interfere with their metabolism. This involves identifying the nutrients these cells rely on, such as sugar, oxygen, or fats, and interfering with these dependencies to impact their survival and growth.
In this thesis, Dominique Sternadt Alexandre Ramos used several approaches to identify and target metabolic weaknesses in AML. She focused partly on repurposing drugs already used to treat other diseases. For instance, she found that metformin, an antidiabetic drug, was particularly effective in AML patients with specific mutations and alterations in fat metabolism. These changes made leukaemia cells more vulnerable to a form of cell death caused by the damaging oxidation of fats. In addition, proteins involved in forming lipid droplets, structures that allow cells to store fats and protect themselves from damage, were investigated.
Additionally, Sternadt Alexandre Ramos combined information about patients’ mutations, proteins, metabolites, and responses to drugs. By examining these different types of information together, she identified specific patterns that could not be detected using just genetics. The results show that studying AML metabolism and integrating multiple data types may help identify new treatment combinations, distinguish relevant patient groups, and guide more personalised treatment decisions.
Find the full thesis here: Targeting metabolic vulnerabilities in acute myeloid leukemia
