dc.contributor.author | Collett, Keon | |
dc.date.accessioned | 2021-07-23T18:25:36Z | |
dc.date.available | 2021-07-23T18:25:36Z | |
dc.date.issued | 2021-07-23T18:25:36Z | |
dc.identifier.uri | http://hdl.handle.net/10222/80616 | |
dc.description.abstract | Infant Leukemia (IL) is a rare and aggressive congenital leukemia that is frequently caused by fusion genes involving lysine methyltransferase MLL (MLL1; KMT2A) and has a dismal prognosis. Further investigation into MLL-fusion disease biology and the role of contributing genetic factors, such as predisposing germline mutations to lysine methyltransferase KMT2C (MLL3), is needed. I genetically engineered two zebrafish models: a Cre/lox inducible transgenic model to express MLL-AF9 or MLL-ENL within specific blood cell lineages, and a knockout model of KMT2C homologs, kmt2ca and kmt2cb. I successfully established three blood cell specific CreERT2 expressing transgenic lines. However, MLL-AF9 and MLL-ENL transgenic fish failed to expression of the MLL-fusion genes and this model requires further development. Preliminary results indicate kmt2cb-/- larvae may have decreased myelopoiesis during primitive hematopoiesis suggesting a block in differentiation, while kmt2ca-/- fish have yet to be assessed. These models represent the development of new tools for IL research. | en_US |
dc.language.iso | en | en_US |
dc.subject | Leukemia | en_US |
dc.subject | MLL | en_US |
dc.subject | Infant | en_US |
dc.subject | KMT2C | en_US |
dc.subject | KMT2A | en_US |
dc.subject | Zebrafish | en_US |
dc.title | Generating Tools to Investigate Infant Leukemia Disease Biology and Identify New Therapies Through Rapid Drug Screening. | en_US |
dc.type | Thesis | en_US |
dc.date.defence | 2020-05-29 | |
dc.contributor.department | Department of Pathology | en_US |
dc.contributor.degree | Master of Science | en_US |
dc.contributor.external-examiner | David Conrad | en_US |
dc.contributor.graduate-coordinator | Paola Mercato | en_US |
dc.contributor.thesis-reader | Todd Druley | en_US |
dc.contributor.thesis-reader | Graham Dellaire | en_US |
dc.contributor.thesis-reader | Clinton Campbell | en_US |
dc.contributor.thesis-supervisor | Jason Berman | en_US |
dc.contributor.thesis-supervisor | Paola Mercato | en_US |
dc.contributor.ethics-approval | Received | en_US |
dc.contributor.manuscripts | Not Applicable | en_US |
dc.contributor.copyright-release | No | en_US |