In the proposed project we will characterize metabolic processes triggered by genetic lesions typical for non-responsive or relapsed patients with acute leukemia in children. It was already described that some mutations found in leukemia patients cause metabolic rewiring which can be a part of neoplastic transformation of normal hematopoietic cells and also could disturb the response to currently used cytostatic drugs. Even the current treatment of childhood acute lymphoblastic leukemia cures more then 80% of patients there are still patients who relapse after the treatment and their outcome is worsened. Relapses are often accompanied with identification of new mutations. We will focus on these particular mutations, prepare leukemia models and study the changes in the metabolic processes. Our team over the last few years established many new techniques which allow us to characterize and study cellular bioenergetic and biosynthetic pathways. We will employ these methods and pursue the aims of he project. This study will be performed also in close collaboration with Academy Of Science of the Czech Republic and international collaborators
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