TAL1 expression and protein targets in T-cell acute lymphoblastic leukemia

In order to better understand the progression of cancer, the changes in genes and their product proteins that lead to malignancy must be studied. This requires the characterization of molecular and genetic interactions that are fundamental to the progression of cancers, such as T-cell acute lymphoblastic leukemia (T-ALL). T ALL is an aggressive cancer that affects both children and adults, and patients typically respond poorly to chemotherapy. In the majority of affected individuals, a specific chromosomal translocation or deletion event leads to the misactivation of TAL1 gene, which produces an aberrantly expressed TAL 1 transcription factor protein. Normally, TALl controls hematopoiesis and blood vessel formation. As a basic helix-loop-helix­transcription factor, TAL 1 heterodimerizes with many other transcription factors and may alter gene activation, gene transcription, and gene product production. It is thought that changes in gene expression patterns, mediated by misexpression of this transcription factor, lead to an overabundance of immature T-cells by deregulating control of cell proliferation and cell death (apoptosis) pathways. Apoptosis pathways are critical to sustaining life, as these beneficial processes allow for the removal of unwanted or abnormal cells through a well-defined series of events. Misexpression of TAL1 in T-ALL may alter transcriptional control and protein expression of one or several genes or proteins that regulate apoptosis, leading to this malignant condition. In this study, Western blot and flow cytometry analyses were used to determine the potential protein targets of TAL 1. In particular, Bcl-xl, caspase-9, and Nur77 were the factors studied. If changes in the expression of these additional proteins, due to altered transcription regulation by TAL 1, can be detected using these methods, then better, more targeted therapies can potentially be developed to combat T-ALL at the molecular level.Thesis (B.?)Honors Colleg