Hematopoietic stem cell senescence and cancer therapy-induced long-term bone marrow injury.

Abstract

Due to improvements in early detection and treatment of cancer, the number of long-term cancer survivors is increasing. Unfortunately, these survivors are at increased risk for developing cancer treatment-related late effects, including ionizing radiation (IR)- and chemotherapy-induced long-term bone marrow (LT-BM) injury. Because LT-BM injury can deteriorate over time or after the patients receiving additional cancer treatment or undergoing autologous BM transplantation, it may eventually lead to the development of hypoplastic anemia or myelodysplastic syndrome. This review is to provide a survey of some of these recent findings regarding the underlying mechanisms by which IR and chemotherapy cause LT-BM injury. Particularly, we will highlight the discoveries of the role of reactive oxygen species in regulating HSC self-renewal and the role of oxidative stress in mediating IR- and chemotherapy-induced HSC senescence and LT-BM injury. These discoveries may lead to the development of new therapeutic strategies that have the potential to reduce the late adverse effects of conventional cancer therapy on the hematopoietic system in long-term cancer survivors.