Functional inactivation of the AF4-MLL oncoprotein

Introduction: We have demonstrated that transduction and recombinant expression of the AF4-MLL oncoprotein in hematopoietic stem/precursor cells is sufficient to induce the development of proB ALL in a mouse model system (Bursen et al., 2010). Results: Here, we present our data on our efforts to functionally inactivate the AF4-MLL fusion protein. First, we targeted the FYRN/FYRC heterodimerization domain, demonstrating that interference with the heterodimerization process leads to proteasomal degradation of AF4-MLL. Next, we investigated Taspase1 which processes the AF4-MLL fusion protein prior to heterodimeriza…