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Show 286 Alesia Trakhimets CHEMOPREVENTION AND TREATMENT OF ZEBRAFISH T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA Alesia Trakhimets, (J. Kimble Frazer) Departments of Pediatrics and Oncological Sciences University of Utah honors college spring 2012 T-lymphoblasts, or T-cells, are blood cells that normally fight viral, fungal, and other infections. T-cell Acute Lymphoblastic Leukemia (T-ALL) is a cancer that is caused by an overgrowth of abnor-mal T-cells. It is an aggressive cancer that progresses quickly if untreated. While effective treat-ments for T-ALL exist, approximately 20% of pediatric and 50% of adult T-ALL patients will later relapse, and most will ultimately die of disease. My project uses zebrafish (Danio rerio) that are prone to developing T-ALL to test investigational agents for T-ALL chemoprevention and treatment. Fish used in this project express Green Fluores-cent Protein (GFP) in their T-cells, making it possible to identify their cancers using a fluorescent microscope. Fish with T-ALL have large GFP+ tumors in the area of the thymus or exhibit GFP throughout their body. Healthy fish have GFP exclusively in their thymus. Lenaldekar (LDK) and HCI-2084 are experimental drugs created at Huntsman Cancer Institute. LDK has an unknown mechanism of action, and HCI-2084 inhibits two receptor tyrosine kinases, Axl and Mer, highly expressed by zebrafish T-ALL cells. We hypothesized that we could test these drugs for their ability to prevent or treat T-ALL. Specifically, we examined whether LDK could prevent T-ALL and whether HCI-2084 could cause regressions of established T-ALL. Drug treatments were performed by housing fish in water containing the agents being tested. To determine if trials were effective, fish were examined weekly by fluorescent microscopy to determine whether new cancers had developed (in LDK trials) or if T-ALL had regressed (in HCI-2084 trials). Dexamethasone, an agent active against T-ALL, was used as a positive control. To date, our results demonstrate that HCI- 2084 is comparable to Dexamethasone in treating zebrafish T-ALL, but LDK is not able to prevent T-ALL. Our findings suggest HCI-2084 is a potential new drug for human T-ALL treatment. J. Kimble Frazer |