Targeted Combination Therapy to Sensitize High-Risk Acute Lymphoblastic Leukemia to Methotrexate via Restoration of Ikaros Tumor Suppression
High-risk B-cell acute lymphoblastic leukemia (B-ALL) frequently recurs after initial treatment and is a lethal disease. "Ikaros" is a cancer fighting protein that prevents leukemia from developing. In children who are diagnosed with high-risk B-ALL, the activity of Ikaros in leukemia cells has been impaired by another protein called CK2. By using a novel medicine that can block the effects of CK2, our laboratory has found that we can restore the cancer fighting ability of Ikaros and kill leukemia cells.
This project will test the novel idea of treating leukemia by combining 1) a medicine to restore the natural ability of the Ikaros protein to prevent leukemia with 2) a standard medicine used to treat the leukemia. We will also study how these drugs are able to work together to produce stronger effects on leukemia. Positive results from this project would lead to a new method of treating B-ALL as well as an entirely new paradigm for developing treatments for other childhood leukemias.