Date of Award
Master of Science (MS)
Cellular, Molecular and Biomedical Sciences
Jessica L. Heath
Hematopoiesis is the complex differentiation process involving the formation of all blood cells from a common progenitor; the hematopoietic stem cell. Errors in this process can lead to acute leukemia, or a rapid accumulation of immature blood cells which hinders proper immune function. While survival rates of this devastating disease have increased dramatically over the last several decades, certain cytogenetic abnormalities remain risk factors for treatment resistance and relapse. One of these abnormalities is a chromosomal translocation involving the transcription factor, AF10
Mix-Lineage Leukemia, Translocated to, 10 (MLLT 10, referred to as AF10) is involved in several oncogenic translocations involved in high-risk leukemia. Functionally characterized as a cofactor of the histone methyltransferase, DOT1L, the extent of AF10 function has not been determined. Examination of AF10 structure and interaction partner, b-Catenin, has lead us to develop a hypothesis regarding the role of AF10 in canonical Wnt signaling. Wnt is a highly complex signaling pathway which plays roles in cell fate determination and self-renewal, and is thought to be vital for the onset and progression of leukemia. We hypothesize that the AF10 fusion protein, CALM-AF10, impacts the normal AF10-b-Catenin interaction, and acts to dysregulate Wnt signaling as a mechanism for promoting leukemia.
We have developed a luciferase reporter system in HEK293T cells by which to test this hypothesis, and utilize immunoprecipitation to investigate the interaction between CALM-AF10 and b-Catenin. We determine through the work of this thesis, that CALM-AF10 upregulates Wnt signaling in a manner independent of an interaction with b-Catenin.
Number of Pages
Deutsch, Jamie Lucille, "Implications of the CALM-AF10 oncogenic fusion protein on Wnt signaling in leukemia" (2020). Graduate College Dissertations and Theses. 1297.
Available for download on Sunday, August 21, 2022