dc.contributor.author | Bentley, Victoria L. | |
dc.date.accessioned | 2016-01-14T18:03:32Z | |
dc.date.available | 2016-01-14T18:03:32Z | |
dc.date.issued | 2016-01-14T18:03:32Z | |
dc.identifier.uri | http://hdl.handle.net/10222/65295 | |
dc.description.abstract | Pediatric T-cell Acute Lymphoblastic leukemia (T-ALL) is a high-risk disease. There is a need for targeted therapies for T-ALL, and techniques to rapidly screen drug candidates and personalize patient therapy. I developed a zebrafish xenotransplantation (XT) model to screen novel agents for efficacy and toxicity. I demonstrated that T-ALL cell lines recapitulate in vitro responses to targeted therapies in vivo. Importantly, patient-derived lymphoblasts engraft in zebrafish and specific drug responses can be quantitatively determined. I identified a mutation sensitive to γ-secretase inhibition in a xenograft from a child with T-cell acute lymphoblastic leukemia, confirmed by Sanger sequencing and validated as a gain-of-function NOTCH1 mutation. Furthermore, I employed the zebrafish XT assay to determine the efficacy of two novel compounds to protect against doxorubicin-induced cardiac damage. The zebrafish XT platform provides a novel cost-effective means of screening novel agents, and tailoring leukemia therapy in real-time to maximize efficacy and minimize toxicity. | en_US |
dc.language.iso | en | en_US |
dc.subject | Zebrafish | en_US |
dc.subject | Leukemia | en_US |
dc.subject | Pediatric cancer | en_US |
dc.subject | Animal models of cancer | en_US |
dc.subject | Acute lymphoblastic leukemia | en_US |
dc.subject | Xenotransplantation | en_US |
dc.subject | Drug screening | en_US |
dc.title | ZEBRAFISH XENOTRANSPLANTATION AS A PRECLINICAL THERAPEUTIC PLATFORM FOR T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA | en_US |
dc.type | Thesis | |
dc.date.defence | 2014-07-07 | |
dc.contributor.department | Department of Pathology | en_US |
dc.contributor.degree | Master of Science | en_US |
dc.contributor.external-examiner | David Anderson | en_US |
dc.contributor.graduate-coordinator | Wenda Greer | en_US |
dc.contributor.thesis-reader | Paola Marcato | en_US |
dc.contributor.thesis-reader | Conrad Fernandez | en_US |
dc.contributor.thesis-supervisor | Graham Dellaire and Jason Berman | en_US |
dc.contributor.ethics-approval | Received | en_US |
dc.contributor.manuscripts | Not Applicable | en_US |
dc.contributor.copyright-release | Not Applicable | en_US |