New insights into mast cell development and contribution to malignant progression - further exploitation of the zebrafish model

Mast cells are blood cells involved in allergic reactions, inflammation and contribute to causing some cancers. Normal mast cell development remains unclear. We took advantage of the transparent zebrafish to study normal mast cell development and model a human mast cell disease called systemic mastocytosis. This disease can be a mild skin rash or evolve into an aggressive leukemia that is currently uncurable. We will use this zebrafish model to find molecular pathways that are activated in this disease and test new treatments. Mast cells may also cause the spread of other cancers due to their involvement in the inflammatory response to cancers. We will make a zebrafish that has fluorescently labeled mast cells and use these fish to study the interaction of mast cells with human tumour cells that we can transplant into the fish. Finally, using our model of systemic mastocytosis, we will complete a genetic screen, which can be done efficiently in zebrafish, to find genes that contribute to causing the more aggressive types of systemic mastocytosis. These experiments will be aided by using the fish with fluorescent mast cells. This work will provide important new information about how abnormal mast cells evolve into leukemia and participate in the progression of other cancers.