Does aging foster transformation to acute myeloid leukemia?
The aim of this study is to test the contribution of aging to foster and 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; 500 in Tromsø and 300 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 Project will take one year longer than previously anticipated With no changes in animal numbers or welfare.
Etterevaluering
The experiment is classified as severe, cf. Regulation on Animal Experimentation, appendix B. A retrospective assessment should be carried out, cf. Instruction for the Food Safety Authority for the administration of the Regulation on Animal Experimentation, § 13.
Begrunnelse for etterevalueringen
The aim of this study has been to test the contribution of aging to foster and drive acute myeloid leukemia (AML).
94 animals were used for various experiments over the whole project.
No transplants were performed. Characterization of the bone marrow niche in old mice were classified as non-recovery. Moderate symptoms of aging in the mice were classified as moderate.
26 mice have been reported with severe classification.
They have either been found dead or have been euthanized according to humane endpoints.
Preliminary data on the role of aging in the development of acute myeloid leukemia and how the bone marrow environment is modified in old mice have been obtained.
Delays in establishing a clean mouse colony led to an absence of results regarding the role of aging in the transformation of bone marrow cells isolated from Nras-G12D donors towards acute myeloid leukemia.
However, nestin-positive cells were sorted from the bone marrow of nes-gfp mice and used for molecular characterization. Preliminary studies of immunophenotyping in aging mice have also been performed.
There is not enough data to conclude on the correct number of animals needed for the main objectives of the project.
Together with KPM in Oslo, refinements in the daily supervision of the mice without too much disturbance were developed. Early signs of disease were followed up with scoring using a specific score sheet for old mice. This score sheet will be incorporated in the continuation of the experiments in Tromsø (FOTS id 24740).
94 animals were used for various experiments over the whole project.
No transplants were performed. Characterization of the bone marrow niche in old mice were classified as non-recovery. Moderate symptoms of aging in the mice were classified as moderate.
26 mice have been reported with severe classification.
They have either been found dead or have been euthanized according to humane endpoints.
Preliminary data on the role of aging in the development of acute myeloid leukemia and how the bone marrow environment is modified in old mice have been obtained.
Delays in establishing a clean mouse colony led to an absence of results regarding the role of aging in the transformation of bone marrow cells isolated from Nras-G12D donors towards acute myeloid leukemia.
However, nestin-positive cells were sorted from the bone marrow of nes-gfp mice and used for molecular characterization. Preliminary studies of immunophenotyping in aging mice have also been performed.
There is not enough data to conclude on the correct number of animals needed for the main objectives of the project.
Together with KPM in Oslo, refinements in the daily supervision of the mice without too much disturbance were developed. Early signs of disease were followed up with scoring using a specific score sheet for old mice. This score sheet will be incorporated in the continuation of the experiments in Tromsø (FOTS id 24740).