Timothy Graubert, MD

The Role of AML/1ETO in the Pathogenesis of t(8;21) Acute Myeloid Leukemia

This year, approximately 10,500 adults will be diagnosed with acute myeloid leukemia (AML) in the U.S. Despite incremental improvements in the care of these patients over the past three decades, most will die of their disease. My laboratory is studying the AML subtype characterized by an exchange of genetic material between chromosomes 8 and 21 which leads to production of a new protein called AML1/ETO. We have generated a new strain of mice that express the human AML1/ETO protein in their bone marrow cells. These mice, unlike strains previously produced by other laboratories, develop a disease that resembles a “preleukemic” syndrome in humans. We are carefully analyzing these mice to determine what AML1/ETO is doing at the molecular level. We will find out whether production of AML1/ETO is just an early event in the development of leukemia, or whether it must remain present at all times for the leukemia cells to survive. To ask this question, we are developing a tool that can specifically shut off the AML1/ETO protein in the mice. If we find that the AML1/ETO protein remains an “Achilles heel” in these cells, this tool could be refined into a novel therapy for AML. Just as new, molecularly targeted therapies have revolutionized the care of patients with chronic leukemias, a better understanding of AML at a molecular level should help us find therapies that are more effective and have fewer side effects.