Summary

Within DKTK, we run the core facility “Xenograft Mouse Models of Acute Leukemias” (https://dktk.dkfz.de/en/sites/muenchen/core_facilities). We transplant primary tumor cells from patients with acute leukemias into severely immuno-compromised mice and use resulting patient-derived xenograft (PDX) cells for genetic engineering with lentiviruses. Expression of recombinant markers in PDX leukemia cells enables bioluminescence in vivo imaging and highly sensitive and reliable monitoring of disease progression and anti-leukemia treatment effects (PLoS ONE 2012 and 2015). Supported by funding of DKTK, we established the model for acute myeloid leukemia (AML). We now perform frequent and highly reliable preclinical treatment trials in individual patient's tumor cells, including models where we induce minimal residual disease using standard polychemotherapy treatment. We also modulate signaling pathways in PDX acute leukemia cells using knockdown or overexpression approaches which enables studying defined signaling molecules on a molecular level in patients' tumor cells in vivo. As core facility, we aim at performing preclinical trials in collaboration with all interested groups and participate in DKTK joint funding projects on acute leukemias.
Beyond that, we are deciphering questions on basic biology in acute leukemias. Funded by a Consolidator Grant of ERC - European Research Council and a Mildred Scheel Professorship of German Cancer Aid, we used recombinant markers to show that PDX acute lymphoblastic leukemia (ALL) cells contain a rare fraction of long term quiescent stem cells which are drug resistant; upon retrieving cells from their in vivo environment, cells start proliferating and become sensitized towards chemotherapy; our data suggest targeting the tumor cell - microenvironment interaction in order to sensitize resistant cancer cells towards anti-cancer treatment (Cancer Cell, 2016).