Our research program aims to identify better predictive markers and targets for the diagnosis and treatment of children with acute lymphoblastic leukemia (ALL) in order to improve the overall outcome and reduce short/long term side effects of chemotherapy. Research activities focus on the pathobiology of leukemia by identifying genetic lesions unique to leukemia and those contributing to cellular drug resistance to both traditional drugs (e.g. prednisolone, L-asparaginase) and precision medicines (e.g. ABL-inhibitors, MEK/ERK-inhibitors). Functional studies address the leukemia-dependency of these lesions and associated signaling pathways. Synergy studies are being conducted in which new (precision) drugs are tested in combination with traditional drugs which form the backbone of childhood ALL treatment.
A second main topic of our research program addresses the interaction between leukemic cells and the bone marrow microenvironment. We noticed that the viability of patients’ ALL cells in co-culture with patients’ mesenchymal stromal cells significantly increases and also affects the level of resistance to (precision) medicines. New communication mechanisms, i.e. tunneling nanotubes, were discovered which contribute to the survival advantage of leukemic cells.
Lentiviral-assisted molecular tool box, next-generation sequencing (Illumina platforms), drug exposure studies, (live-)imaging, proteomics, patient-derived ALL xenograft (PDX) and PDX/hMSC scaffold mouse models, in vivo proof-of-concept studies, biomarker analysis in phase I, II and III clinical trials.