In Vivo Effects of Valporic Acid and Dexamethasone on Zebrafish T-Cell Leukemia

Valporic Acid (VPA) and Dexamethasone (DXM) is effective in T-ALL, combination of both will produce a synergistic effect. Zebrafish (Danio rerio) mis-expressing human MYC (hMYC) protein, develop T cell acute lymphoblastic leukemia (T-ALL) and they develop tumors that originate in the thymus and spread throughout the body. These fish have also been engineered to express green fluorescent protein (GFP) in their body. Consequently, their cancers are fluorescent and can be viewed with a special microscope. To test both VPA and DXM in zebrafish T-ALL, we placed both drugs in tanks of water housing hMYC fish with T-ALL. We monitor them over a two week interval using serial fluorescent microscopy to observe any tumor regressions. With several trial runs of each drug, we found a minimal 10% reduction in tumor cells in the fish and have proceeded on to the combination trial of DXM and VPA with the minimal concentration levels of both. We identified appropriate concentrations of both VPA and DXM that have an effect on zebrafish T-ALL. When used in combination, they will form a potent form of treatment.