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The SDF1âº-CXCR4 axis is a major chemo-attractant mechanism for pre-B ALL cells that promotes migration and adhesion to stromal cells. Our studies showed that inhibition of binding of SDF1âº to CXCR4 with small molecule inhibitors chemo-sensitizes the leukemia cells in tissue culture and in mouse models.
An important step towards the development of new therapies for cancer is identifying cell surface molecules that have restricted expression or ideally have expression only on the target cancer cell. Our studies were the first to identify expression of the BAFF-R on the surface of many pre-B ALL samples and to make use of this to explore different forms of therapy including the application of NK cells.
Galectins are carbohydrate-binding proteins with immune-modulatory properties. We discovered that when pre-B ALL cells develop insensitivity to drugs when protection is provided by the presence of stromal cells, the leukemia cells have radical changes in the expression of many genes related to inflammatory processes. One of these is Galectin-3. However, under non-stressed conditions, pre-B ALL cells do not synthesize their own Galectin-3 and all the Galectin-3 present in and on these cells is provided by the protective stromal cells. Thus Galectin-3 is one of the molecular mediators of a two-way communication between the leukemia and the microenvironment.