Project
ProSteR: Radiation-induced leukaemia in children: response of hematopoietic stem cells to photon and proton therapy (ProSteR)
Epidemiological studies have highlighted that leukemia can be considered as the most important
malignancy after radiation exposure during childhood. The high risk is related to the high sensitivity
of the bone marrow at young ages. Since the red bone marrow harbors hematopoietic stem and
progenitor cells (HSPCs), a better understanding of the response to protons and photons of these
HSPCs is warranted, particularly in the context of pediatric proton therapy (PT). The clinical
application of PT is of great interest for pediatric patients due to the optimal dose distribution and
the lower integral whole body dose compared to conventional x-ray radiotherapy (i.e. photon
therapy), resulting in a reduction of side effects. Despite some degree of normal tissue injury is still
inevitable, radiotherapy for pediatric cancer is a life-saving procedure. Currently, there is little
information available on the response of HSPCs to proton therapy. In this project, radiobiological
differences between proton and conventional x-ray (photons) exposure of HSPCs will be
investigated together with the underlying mechanisms for the high radiosensitivity of HSPCs in vitro
and in vivo. The results will help estimate HSPC damage in radiotherapy-treated children, provide
opportunities to improve treatment strategies in pediatric radiotherapy and enable better
secondary leukemia risk estimations for childhood cancer survivors.