Attenuated DNA damage repair delays therapy-related myeloid neoplasms in a mouse model.

ABSTRACT: Therapy-related cancers are potentially fatal late life complications for patients who received radio- or chemotherapy. So far, the mouse model showing reduction or delay of these diseases has not been described. We found that the disruption of Aplf in mice moderately attenuated DNA damage repair and, unexpectedly, impeded myeloid neoplasms after exposure to ionizing radiation (IR). Irradiated mutant mice showed higher rates of p53-dependent cell death, fewer chromosomal translocations, and a delay in malignancy-induced mortality. Simultaneous deficiency of p53 abrogated IR-induced apoptosis and the benefit of impaired DNA repair on mortality in irradiated Aplf–/– mice. Depletion of APLF in non-tumorigenic human cells also markedly reduced the risk of radiation-induced chromosomal aberrati

SUBMITTER: Tong KI 

PROVIDER: S-EPMC5133969 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature