Neuroglial Regulation of the Haematopoietic Stem Cell Niche in Acute Myeloid Leukaemia Transformation

The aim of this study is to test the contribution of the neural dysfunction of the bone marrow microenvironment to drive AML, and the therapeutic potential of the reversion of this damage. This project is a continuation of FOTS 7922 to confirm preliminary data with optimized protocols. The expected harmful effect on the animals are mild to transiently severe, only in transplanted mice. The present research will provide with insights into the basic processes that underlie HSC dysfunction and pinpoint a novel therapy against AML. Haematopoiesis has been best characterized in the mouse system and the interaction of the haematopoietic stem cell with its microenvironment can only be studied in vivo, due to the insufficient knowledge of the microenvironment. Number of animals are kept to a minimum (480) consistent with the obtention of statistically meaningful results. Mice will be used in the most efficient way possible, attempting to obtain the maximum information from each experimental animal. When assays cannot be performed immediately, cells will be cryopreserved whenever possible. Mice will be sacrificed at time points when they will only show haematological symptoms of disease. It is not the goal of this study to analyze terminal stages of disease, but identify the role of the nervous system before severe symptoms develop aiming at uncovering early therapeutic targets against agressive AML.