Patients with leukemia require new and better medicines. While current drug treatments can often clear most leukemia cells from the body, too often the disease will become resistant. We believe that it is important to find new drugs that target the parts of cancer cells that control how and when specific cancer genes are turned on or off. These systems work at regions of our genome called ‘enhancers’. Enhancers represent the most important circuits of our genome by coordinating what genes are on or off. In cancers like leukemia these circuits are broken. This leads to an altered state of unrestrained growth, survival under stress, and resistance to drugs. In leukemia cells there are many mutations in genes that change how enhancers work, but few drugs to target them. We need a complete toolbox of enhancer-targeting drugs and we are making significant progress – but more work is needed to understand how these drugs work in order to identify the patients most likely to benefit. Our goals with this project are to use new genomics tools to study the effects of a new class of enhancer-targeting drugs that directly block critical signaling factors. These drugs have not yet been studied in leukemia, and we expect that our efforts will lead to future use of this promising new type of medicine.