Grant: Operating Grant

It is widely accepted that cancer is a multistep process associated with the activation or inactivation of certain cancer genes. In our laboratory, we are using multistage erythroleukemias induced by Friend virus as a model to identify and characterize genes associated with leukemia development. Toward this goal, we have previously isolated several genes whose activations or inactivations have been shown to be involved in the induction and progression of erythroleukemia (cancer of red blood cells). These genes have also been shown to be involved in other types of human cancers. In a recent development, we have also discovered that the spleen, a site of tumor migration, supports proliferation and expansion of leukemic cells. Moreover, we have shown that a unique population of primitive blood cells can delay tumor progression when injected into the leukemic mice. We provide evidence to suggest that these unique blood cells inhibit leukemia progression through the induction of changes in the tumor microenvironment. The experiments described in this research proposal are designed to characterize the components of the microenvironment capable of inhibiting tumor progression and identify strategies to promote a tumor inhibitory niche toward the clinical treatment of leukemia. Therefore, we plan to first characterize the leukemic inhibitory cells from both mouse and human by isolating them using advanced cell culture methods. We will also examine whether injection of various factors into mice is capable of expanding these leukemic inhibitory cells. Overall, these studies should provide important insight into the role of the microenvironment in the progression of leukemia that can eventually be used for the development of more efficient treatments for leukemia and other cancers.