6A. ALL, leukemic niche and oncogenomics

The Den Boer group has expertise in so-called pathobiological studies addressing which (combination of) genetic lesions characterize the patients’ leukemic cells, how these lesions functionally contribute to therapy resistance and how these lesions affect the behavior of leukemic cells and the interaction with the bone marrow microenvironment. Our most recent studies showed that leukemic cells manipulate stromal supportive tissues by a direct cell-cell interaction. This interaction provides leukemic cells a way to escape from (targeted) drugs. We hypothesize that this stromal interaction will also affect the interaction of leukemic cells with normal immune cells since we observed that cytokine and chemokine levels changed upon this interaction. We are exploring the immunoregulatory aspects of the leukemic niche, since this may point to ways to kill leukemic cells more specifically, also given the emerging role for immunotherapeutic strategies like targeting leukemic cells with engineered CAR-T cells and bi-specific antibodies (BiTEs).

The new PhD student will study the interaction between leukemic cells and normal immune cells in the context of the bone marrow microenvironment. The candidate will a.o. manipulate factors that are changed upon close contact between leukemic cells and bone marrow derived stromal cells. Key technologies that will be used are multiparameter flow cytometry, flow sorting, imaging and manipulating leukemic cell and normal immune cell interactions and addressing vulnerability to (immune)modulatory agents in ex vivo multidimensional models.