Acute myeloid leukemia (AML) is a very aggressive cancer. The median age of AML patients is 68 years old, and only 10% of those over age 60 survive this cancer. AML is initiated and maintained in patients by leukemic stem cells (LSC). These are cells that can produce more leukemic cells in a process called self-renewal, but also produce slightly more differentiated cells, which make up the bulk of the leukemia. In order to cure AML, it is necessary to eliminate or control the LSC as well as the bulk population. Unfortunately, each individual AML patient has several different genetic kinds of leukemic cells in their cancer, and these leukemic cells can expand or diminish in numbers based on their environment in the bone marrow and other pressures, such as inflammation or therapy. Our recent findings also suggest that one type of genetic leukemic cell may help support other types of leukemic cells, and we have developed a model that allows us to examine the interactions between these different types of leukemic cells. Using biochemical assays, single cell sequencing and functional studies, we are currently investigating how loss of function of a specific gene alters cell signals such that some of these signals leave the cell and allow other leukemic cells to expand using cell and animal models. We are also examining cells from AML patients and tracking their response to manipulation of the signals we have identified. We hope that this work will provide information on how to target these specific signals to improve treatments for AML