DYRK1A is a novel target in B-Cell leukemia

We will use bothgenetic and pharmacologic approaches to determine the requirement for DYRK1A in malignant B-cells. Ourgoal is to generate pre-clinical data to support further development of DYRK1A inhibitors as a new therapy.Aim 2: Identify the mechanisms by which DYRK1A inhibition causes growth inhibition of ALL cells.We will first study the manner in which the inhibitors impede the growth of ALL cells and assess whetherreduced phosphorylation of caspase 9, a known substrate of DYRK1A, contributes to increased cell death of theleukemia cells. Second, we will use an unbiased approach to identify novel substrates of DYRK1A in ALLcells.Our long-term goal is to test DYRK1A kinase inhibitors in pre-B ALL in a Phase I study.