Leukemic niche

We discovered a pro-survival communication mechanism which depends on direct contact between leukemic cells and the bone marrow support cells. Together this creates an ALL-educated niche in which stromal support cells are being instructed to produce pro-leukemic factors that maintain the vitality of leukemic cells. The nature of these factors depends on the genomic lesions characterizing the leukemia, showcasing how the oncogenomic and leukemic niche research lines benefit from each other. E.g. ETV6::RUNX1 positive ALL cells elicited an interferon α/β response in stromal support cells that most likely has immune-modulating effect in the local bone marrow microenvironment (Smeets, Haematologica 2024). This latter is part of ongoing research and will result in knowledge about factors driving resistance of leukemic cells in the bone marrow niche. This work is also of high interest to tackle the way leukemic cells escape from immunotherapies like CAR-T and T-cell engaging antibodies (e.g.blinatumomab, but also to drug-conjugated antibodies (e.g. inotuzumab). To study the effect of the leukemic niche on response to immunotherapy we are developing 3D bone marrow models that are scalable and reproducible and can be used to study the effect of (immunomodulatory) drugs in the interaction between leukemic cells, healthy immune cells and the bone marrow supportive cells. Our combined knowledge about the dynamics in the leukemic bone marrow niche, drug resistance and pathobiology/genetic lesions in leukemic cells is unique and may lead to innovative ways to improve the treatment of children with ALL.