6B. Oncogenetic lesions affecting susceptibility to (immuno)therapy in ALL (project 6B)

The Den Boer research group studies the way (new) genetic lesions can improve the diagnosis and treatment given to children with newly diagnosed B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Our 25-year track record in this field has resulted in genetic markers and (precision) medicines being implemented in new treatment protocols, and our journey continues to further improve the specificity of anti-leukemia treatment. Our studies address which (combination of) genetic lesions contribute to therapy resistance and how resistance can be circumvented or reversed. Our recent studies revealed that the bone marrow microenvironment contributes to therapy resistance by offering an escape route to leukemic cells by which they can reduce intracellular drug levels.

The new PhD student will study the way the bone marrow microenvironment is being manipulated by the oncogenetic lesions found in leukemic cells and whether this provides ways to interfere and reverse resistance to known chemotherapeutic and targeted drugs or to modulate the response to new immunotherapeutic approaches. Key technologies that will be used are single cell sequencing (CITE-seq), multiparameter flow cytometry, flow sorting, (lentiviral) gene transductions, confocal and widefield imaging, and patient-derived xenograft models for drug efficacy studies.