Targeting MLL-Cofactor Interaction to Selectively Block Mixed Lineage Leukemia
Leukemia often occurs due to chromosomal breakage, which results in mutations that cause blood cells to grow in a disordered and uncontrolled manner. One gene that is often involved in chromosomal translocations that occur in childhood leukemia is the MLL (Mixed Lineage Leukemia) gene. Conventional chemotherapy is very ineffective at curing this disease, and as a consequence most patients relapse. Using a mouse model, Dr. Ernst’s lab has shown that the normal (wild-type) mouse MII gene is essential for maintaining the growth of blood cells. The normal MLL protein operates as part of a complex, with several essential cofactors or facilitating proteins. They are investigating whether blocking the interaction between MLL and its cofactors will selectively kill leukemia cells. Some cofactors have been shown to be essential for the leukemia to develop after expression of MLL fusion oncogenes. This lab will use several genetically engineered mouse models to study the effects of removing these cofactors on normal blood cell development. This comparative analysis will identify genetic pathways that can be exploited to find new ways to treat leukemia.