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Our blood system is maintained by unique blood-forming stem cells in the bone marrow that are responsible for producing mature blood cells throughout life. Different types of blood stem cells with different properties have been demonstrated. The unique characteristics are determined by specific genes, which are regulated by so-called epigenetic factors. Disturbances in the activity of the genes, such as mutations, can lead to the regulation changing and the blood stem cells becoming malignant. Malignant stem cells can cause leukemias. BCR-ABL is an oncogene that can cause chronic myeloid leukemia or acute lymphoblastic leukemia. Why the same oncogene leads to different types of leukemia is unclear. The detection of different types of blood stem cells with different biological properties suggests that different types of blood cancer can occur depending on which blood stem cell type the cancer originates from. In this research program, this will be tested by overexpressing the oncogene BCR-ABL1 in different blood stem cell groups to evaluate whether different leukemia types develop. Furthermore, the epigenetic regulation of the blood stem cells will be modified to determine if this change can influence leukemia development. The studies will be carried out with various mouse models, transplantation experiments and mapping of gene expression and epigenetic profiles in the blood stem cells. The goal is to evaluate whether oncogene activation in different stem cell types leads to the development of different leukemias, as well as leads to different leukemia processes within the same disease. These studies are of great importance, above all because it has not previously been studied with different blood stem cell types. This research will provide increased understanding of the role of blood stem cell functions in leukemia development, which is important to be able to prevent the occurrence of leukemias in the future. In addition, the studies will contribute important knowledge that can form the basis for future development of better and earlier diagnostic and treatment options for patients.

Our blood system is maintained by unique blood-forming stem cells in the bone marrow whose task is to produce mature blood cells throughout their lives. Various types of blood stem cells with different properties have been demonstrated. The unique properties of blood stem cells are determined by specific genes regulated by so-called epigenetic factors. Disturbances in the activity of the genes such as mutations can lead to changes in the regulation of the blood stem cells. These changes can contribute to the onset of blood cancer. Knowledge of how normal blood stem cells work and how epigenetic factors regulate this function can increase our understanding of how and why blood cancer develops. The detection of various types of blood stem cells with different biological properties in the blood system suggests that different types of blood can occur depending on the blood stem cell type of the cancer. In this research program, the epigenetic factors that control and regulate different blood stem cell types and their function will be identified. Furthermore, this information will be used to study the difference in how blood cancer develops from different blood stem cells. This will be achieved through a series of studies involving mouse models, genetic and molecular biological methods. An increased understanding of the basic mechanisms of blood stem cell functions is very important in order to understand and prevent the emergence of various types of blood diseases such as leukemias. These studies are of great importance especially because mutations in epigenetic factors have been detected in normal healthy blood stem cells. These changes are associated with precursors of blood cancer and may lead to a greater risk of suffering from blood disorders. In addition to an increased understanding of blood stem cell functions, these studies will thus also contribute to the development of better and earlier diagnostic and treatment options for patients.

Our blood system is maintained by unique blood-forming stem cells in the bone marrow whose task is to produce mature blood cells throughout their lives. Various types of blood stem cells with different properties have been demonstrated. The unique properties of blood stem cells are determined by specific genes regulated by so-called epigenetic factors. Disturbances in the activity of the genes such as mutations can lead to changes in the regulation of the blood stem cells. These changes can contribute to the onset of blood cancer. Knowledge of how normal blood stem cells work and how epigenetic factors regulate this function can increase our understanding of how and why blood cancer develops. The detection of various types of blood stem cells with different biological properties in the blood system suggests that different types of blood can occur depending on the blood stem cell type of the cancer. In this research program, the epigenetic factors that control and regulate different blood stem cell types and their function will be identified. Furthermore, this information will be used to study the difference in how blood cancer develops from different blood stem cells. This will be achieved through a series of studies involving mouse models, genetic and molecular biological methods. An increased understanding of the basic mechanisms of blood stem cell functions is very important in order to understand and prevent the emergence of various types of blood diseases such as leukemias. These studies are of great importance especially because mutations in epigenetic factors have been detected in normal healthy blood stem cells. These changes are associated with precursors of blood cancer and may lead to a greater risk of suffering from blood disorders. In addition to an increased understanding of blood stem cell functions, these studies will thus also contribute to the development of better and earlier diagnostic and treatment options for patients.