Journal article
Brain Development and Heart Function after Systemic Single-Agent Chemotherapy in a Mouse Model of Childhood Leukemia Treatment
Clinical cancer research, Vol.24(23), pp.6040-6052
12/01/2018
DOI: 10.1158/1078-0432.ccr-18-0551
PMID: 30054283
Abstract
Chemotherapy for childhood acute lymphoblastic leukemia (ALL) can cause late-appearing side effects in survivors that affect multiple organs, including the heart and brain. However, the complex ALL treatment regimen makes it difficult to isolate the causes of these side effects and impossible to separate the contributions of individual chemotherapy agents by clinical observation. Using a mouse model, we therefore assessed each of eight representative, systemically-administered ALL chemotherapy agents for their impact on postnatal brain development and heart function.
Mice were treated systemically with a single chemotherapy agent at an infant equivalent age, then allowed to age to early adulthood (9 weeks). Cardiac structure and function were assessed using
high-frequency ultrasound, and brain anatomy was assessed using high-resolution volumetric
MRI. In addition, longitudinal
MRI was used to determine the time course of developmental change after vincristine treatment.
Vincristine, doxorubicin, and methotrexate were observed to produce the greatest deficiencies in brain development as determined by volumes measured on MRI, whereas doxorubicin, methotrexate, and l-asparaginase altered heart structure or function. Longitudinal studies of vincristine revealed widespread volume loss immediately following treatment and impaired growth over time in several brain regions.
Multiple ALL chemotherapy agents can affect postnatal brain development or heart function. This study provides a ranking of agents based on potential toxicity, and thus highlights a subset likely to cause side effects in early adulthood for further study.
Details
- Title: Subtitle
- Brain Development and Heart Function after Systemic Single-Agent Chemotherapy in a Mouse Model of Childhood Leukemia Treatment
- Creators
- T Leigh Spencer Noakes - Translational Medicine, The Hospital for Sick Children Research Institute, Toronto, Ontario, CanadaThomas S Przybycien - Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, CanadaAmanda Forwell - The University of Waterloo, Waterloo, Ontario, CanadaConnor Nicholls - The University of Waterloo, Waterloo, Ontario, CanadaYu-Qing Zhou - Ted Rogers Centre for Heart Research, Translational Biology and Engineering Program, The University of Toronto, Ontario, CanadaDarci T Butcher - Genetics & Genome Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, CanadaRosanna Weksberg - Institute of Medical Sciences, The University of Toronto, Toronto, Ontario, CanadaSharon L Guger - Department of Molecular Genetics, The University of Toronto, Toronto, Ontario, CanadaBrenda J Spiegler - Department of Pediatrics, Faculty of Medicine, The University of Toronto, Toronto, Ontario, CanadaRussell J Schachar - Psychiatry Research, The Hospital for Sick Children, Toronto, Ontario, CanadaJohann Hitzler - Development and Stem Cell Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, CanadaShinya Ito - Pharmacology and Toxicology, Faculty of Medicine, The University of Toronto, Toronto, Ontario, CanadaEllen van der Plas - Department of Psychiatry, The University of Iowa Hospital and Clinics, Iowa City, IowaBrian J Nieman - Ontario Institute for Cancer Research, Toronto, Ontario, Canada
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.24(23), pp.6040-6052
- Publisher
- United States
- DOI
- 10.1158/1078-0432.ccr-18-0551
- PMID
- 30054283
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Grant note
- CIHR
- Language
- English
- Date published
- 12/01/2018
- Academic Unit
- Psychiatry
- Record Identifier
- 9984003444602771
Metrics
23 Record Views