Chemotherapy-induced cellular senescence suppresses progression of Notch-driven T-ALL

Autoři: Ying Zhang aff001;  Justin Gundelach aff001;  Lonnie D. Lindquist aff001;  Darren J. Baker aff002;  Jan van Deursen aff002;  Richard J. Bram aff003
Působiště autorů: Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, United States of America aff001;  Department of Pediatric and Adolescent Medicine, and Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, United States of America aff002;  Department of Immunology, and Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, United States of America aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article


T cell acute lymphoblastic leukemia (T-ALL) is a serious hematologic malignancy that occurs in children and young adults. Current therapies include intensive chemotherapy and ionizing radiation that preferentially kill malignant cells. Unfortunately, they are frequently accompanied by unintended negative impacts, including the induction of cellular senescence and long-term toxicities in normal host tissues. Whether these senescent cells resulting from therapy increase the susceptibility to relapse or secondary cancers is unknown. Using transgenic and pharmacological approaches to eliminate doxorubicin-induced senescent cells in a Notch-driven T-ALL relapse mouse model, we find that these cells inhibit tumor recurrence, suggesting that senescence in response to treatment suppresses tumorigenesis. This finding, together with extensive evidence from others demonstrating that age-associated health problems develop dramatically earlier among childhood cancer survivors compared to age-matched counterparts, suggests a relationship between therapy-induced senescence and tumorigenesis. Although cancer risk is increased through accelerated premature-aging in the long run, therapy-induced senescence appears to protect survivors from recurrence, at least in the short run.

Klíčová slova:

Aging – Aging and cancer – Cancer treatment – Cell staining – Drug therapy – Leukemias – Mouse models – Senescence


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2019 Číslo 10
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