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

Autor: Jan M. van Deursen, Justin H. Gundelach, Richard J. Bram, Ying Zhang, Darren J. Baker, Lonnie D. Lindquist
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Aging
Physiology
Epidemiology
Aging and Cancer
Cancer Treatment
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
medicine.disease_cause
Hematologic Cancers and Related Disorders
Mice
0302 clinical medicine
Medicine and Health Sciences
Young adult
Receptor
Cellular Senescence
Staining
Antibiotics
Antineoplastic
Multidisciplinary
Receptors
Notch
Pharmaceutics
Cancer Risk Factors
Cell Staining
Animal Models
Hematology
3. Good health
Leukemia
Cell Transformation
Neoplastic
medicine.anatomical_structure
Experimental Organism Systems
Oncology
030220 oncology & carcinogenesis
Disease Progression
Medicine
Female
Research Article
Senescence
T cell
Transgene
Science
Cellular senescence
Mouse Models
Research and Analysis Methods
03 medical and health sciences
Model Organisms
Drug Therapy
Leukemias
medicine
Animals
business.industry
Biology and Life Sciences
Cancers and Neoplasms
medicine.disease
030104 developmental biology
Specimen Preparation and Treatment
Doxorubicin
Medical Risk Factors
Animal Studies
Cancer research
Neoplasm Recurrence
Local
Physiological Processes
business
Carcinogenesis
Organism Development
Developmental Biology
Zdroj: PLoS ONE, Vol 14, Iss 10, p e0224172 (2019)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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