Inhibition of Runx1 Tyrosine Phosphorylation in the Treatment of Human Leukemia
Normal gene expression is controlled by proteins, called transcription factors, which bind to DNA and turn on or off nearby genes. Mutations in transcription factors occur frequently in cancer, leading to disordered gene expression. The transcription factor Runx1 is one of the most common mutated genes in human leukemias, accounting for ~20-25% of cases. In many of these leukemias, the residual Runx1 activity is either inhibited or is insufficient to promote normal cell maturation. The Cantor laboratory recently discovered that a group of enzymes, called tyrosine kinases, modify Runx1 and inhibit its function. Importantly, drugs that block the activity of this class of tyrosine kinases are under active clinical development, or have already been approved, for the treatment of other types of cancer. This proposal explores the potential use of these drugs to enhance residual Runx1 activity as complementary treatment for Runx1 related human leukemias.