Cancer therapy-induced residual bone marrow injury-Mechanisms of induction and implication for therapy.

Current Cancer Therapy Reviews
Yong WangDaohong Zhou

Abstract

Bone marrow (BM) suppression is the important dose-limiting side effect of chemotherapy and radiotherapy for cancer. Although acute myelosuppression is an immediate concern for patients undergoing cancer therapy, its management has been improved significantly in recent years by the use of various hematopoietic growth factors. However, many patients receiving chemotherapy and/or ionizing radiation (IR) also develop residual (or long-term) BM injury (a sustained decrease in HSC reserves due to an impairment in HSC self-renewal) after the recovery from acute myelosuppression. Unlike acute myelosuppression, residual BM injury is latent and long lasting and shows little tendency for recovery. Following additional hematopoietic stress such as subsequent cycles of consolidation cancer treatment or autologous BM transplantation, residual BM injury can deteriorate to become a hypoplastic or myelodysplastic syndrome. This article review some of the new developments in elucidating the cellular and molecular mechanisms whereby chemotherapy and radiotherapy cause residual BM injury. Particularly, we discuss the role of induction of hematopoietic stem cell (HSC) senescence via the p53-p21(Cip1/Waf1) and/or p16(Ink4a)-RB pathways in the induc...Continue Reading

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