B-cell acute lymphoblastic leukemia (B-ALL) represents a collection of diseases that are categorized into subtypes based on the presence of recurrent cytogenetic abnormalities. These abnormalities often result in the expression of oncogenic drivers that denote a standard- or
high-risk for relapse. Currently, survival rates boarder 40% for adult patients and relapses are often observed in patients lacking high-risk markers. Thus, there is an unmet need for biomarkers that can identify all high-risk leukemia, and development of novel therapies based on a better understanding of the molecular drivers of B-ALL. To address this need, I designed a multi-parameter phospho-flow cytometry platform and characterized basal and cytokine-potentiated signaling in adult B-ALL samples. I identified patterns of cytokine-responsiveness across B-ALL patients that correlated with the presence of high-risk oncogenic drivers. Furthermore,
I demonstrated that small-molecule inhibitors could abrogate cytokine-induced signaling in
high-risk patients suggesting these inhibitors may compliment current chemotherapeutic protocols.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33296 |
| Date | 20 November 2012 |
| Creators | Kraguljac, Alan P. |
| Contributors | Danska, Jayne, Guidos, Cynthia J. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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