Does aging foster transformation to acute myeloid leukemia? (transfer to Tromsø)
The aim of this study is to test the contribution of aging to drive AML. The expected harmful effect on the animals are mild to transiently severe, in transplanted mice. The present research will provide with insights into the basic processes that underlie HSC dysfunction and the role of aging foster transformation to 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 (800 recipients; 706 in Tromsø, 94 in Oslo; 40 donors -FOTS8408) consistent with the obtention of statistically meaningful results. The 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 contribution of aging process to transformation to AML before severe symptoms to understand if aging forters transformation to AML. Due to delays caused by AKM closing Down in Tromsø, the pandemic, and the move back from Oslo the Project will take three years longer than previously anticipated With no changes in animal numbers or welfare.
Etterevaluering
The Norwegian Food Safety Authority must retrospectively assess all severe experiments.
Begrunnelse for etterevalueringen
Despite not having been able to perform bone marrow transplant from healthy or pre-leukemic mice in young and old animals, we have been able to use old mice for FACS-sorting of nestin-positive mesenchymal stromal cells for gene expression analysis. Our first results show that these cells express high levels of Sucnr1, which may represent a novel pathway used by these cells to control hematopoiesis in health and malignancy that we will follow up in future work.
Animals used only for in vitro analysis (sorting of cells) are classified as non-recovery, they were old but in good shape according to strict monitoring. Animals euthanized due to health issues informed per score sheet were classified as moderate, and terminated before they reached a severe state.
We always use in vitro and ex vivo experiments when appropriate, before performing in vivo experiments; transplantation is only performed by experienced researchers; and animals are followed up closely with use of score sheets. We have a refined geriatric score sheet that works well. As a recent improvement, the conditions are kept sterile starting one week before performing the transplant in this and all our current FOTS. This measure was not taken here as mice were not irradiated/transplanted.
Animals used only for in vitro analysis (sorting of cells) are classified as non-recovery, they were old but in good shape according to strict monitoring. Animals euthanized due to health issues informed per score sheet were classified as moderate, and terminated before they reached a severe state.
We always use in vitro and ex vivo experiments when appropriate, before performing in vivo experiments; transplantation is only performed by experienced researchers; and animals are followed up closely with use of score sheets. We have a refined geriatric score sheet that works well. As a recent improvement, the conditions are kept sterile starting one week before performing the transplant in this and all our current FOTS. This measure was not taken here as mice were not irradiated/transplanted.