Stem Cell Metabolic Dysfunction in Myeloid Leukaemia and its Therapeutic Targeting

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia occurring in adults. Its incidence increases with age and the prognosis for the older patient remains bleak. Overcoming these problems will require a better understanding of AML. Interestingly, cancer and normal cells differ in their metabolism that is their way of obtaining energy. Alterations in different steps of metabolic pathways link to cancer development and resistance to therapies. Furthermore, surrounding or distal normal cells can sense metabolic disturbances in cancer cells through sensing of metabolic intermediates, usually present inside the cell but released outside under particular conditions such as metabolic stress. These pathways have received little attention in the context of leukaemia. The primary aim of this project is to investigate the potential role of metabolic intermediate signalling dysfunction in AML pathogenesis and its importance to human AML. Human patient material will be used for this study, and data will be validated in vivo using genetically engineered mouse models expressing AML driver genes. Specific metabolic intermediates will be controlled in vivo using drugs and additional genetic engineering, allowing their potential value to be tested in novel therapeutic strategies. Further, we will discriminate the contribution of normal regulatory cells. Thus, the present research will give insights into the basic processes that regulate blood stem cell function/dysfunction, and will allow the application of this knowledge to provide a novel platform for more efficient therapies against AML.

This project has received funding from the Research Council of Norway (FRIPRO Program) - Young Research Talent, 2016-2020


Ansvarlig for prosjektet: Lorena Arranz