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| The blood forming system is maintained by a population of hematopoietic (blood forming) stem cells (HSCs). The HSCs guarantee life-long blood production and regeneration after chemotherapies or bone marrow transplantation. In spite of its robustness to perturbations, hematopoiesis can be outcompeted by leukemias which lead to expansion of malignant cells. Leukemias are maintained by a small but heterogeneous population of leukemic stem cells (LSCs) that resist treatment and trigger relapse.
We propose different multi-compartment models of cell differentiation. The models consist of nonlinear systems of ordinary differential equations describing time evolution of healthy and cancerous cell populations subjected to different possible feedbacks. Mathematical results and simulations are discussed based on patient data.
The models will be applied to better understand outcompetition of hematopoiesis by leukemic cells, possible impacts of LSC properties on the course of the disease, changes of cell properties due to clonal competition, and interindividual differences in responses to treatment. Estimation of LSC properties and simulation of chemotherapy and bone marrow transplantation may help to discuss mechanisms of relapse and effective treatment strategies. |
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