In vivo-Modelle der Leukämogenese
Acute Lymphoblastic Leukemia (ALL) is one of the major causes of mortality and morbidity among children. A better understanding of the molecular pathogenesis involved in ALL has revealed several diseases-associated biomarkers that can be targeted. The overall aims of our group is to understand the role of exposure to infection in the etiology of childhood acute lymphoblastic leukemia and secondly the development of novel drugs, which specifically target leukemic cells.
Project: Exposure to infection in childhood acute leukemia
Acute leukaemia is the most common cancer in childhood and the incidence is increasing especially in socio economic high standard countries. Infection as a trigger of leukaemia development in children has been controversially discussed since decades and leukaemia occurrence in time-space cluster supports this hypothesis. However experimental evidence, which proves the connection of exposure to infection and childhood leukaemia is rare. We and colleagues have established and characterized two genetically modified mouse models representing classical subtypes of childhood leukaemia (Pax5+/- and TEL-AML1). The mice develop acute lymphoblastic leukaemia only after exposure to a common infection environment and represent a very similar phenotype as compared to acute lymphoblastic leukaemia in childhood. This work offers for the first time novel insight in the role of infection in leukaemia development and offers novel approaches for leukaemia prevention.
Project: Novel targeted therapy in childhood acute leukemia
We develop novel and individual drug targets and therapies for resistant leukemia in childhood, which still have a poor prognosis. Novel compounds are designed and synthesized by our collaborators. These compound libraries as well as a variety of clinically approved drugs are then tested for their potency and selectivity in acute lymphoblastic leukemia. We perform a series of biochemical and functional in vitro assays with the selected compounds while the most potent candidate is subjected to in vivo analysis using Xenograft mouse models.
- Deutsche Jose Carreras Leukämie Stiftung
- Deutsche Kinderkrebsstiftung
- DKTK joint funding
- Elterninitiative Kinderkrebsklinik