New Investigator Research Grant Program

Every year, hundreds of men diagnosed with acute myeloid leukemia (AML), a cancer of the blood and bone marrow, are found to have lost their Y chromosome in their leukemia cells. For over 40 years, doctors have dismissed this finding as meaningless, assuming the Y chromosome has no role beyond determining sex. Our research shows this assumption is wrong. We discovered that Y chromosome loss fundamentally changes how leukemia cells behave: it alters their gene activity, reshapes how they interact with the immune system, and makes them more responsive to chemotherapy. Importantly, the Y chromosome is lost only in the cancer cells while the patient's healthy immune cells keep their Y chromosome, meaning this change is driven by the leukemia itself. In this project, we will identify exactly which genes on the Y chromosome control these effects and determine whether women who lose an X chromosome in their leukemia cells experience similar changes. We will study a specific type of AML where both Y and X chromosome loss are common, allowing us to test whether these changes follow a shared biological mechanism. Our goal is to develop a blood test that can detect this biology in patients, helping doctors make better treatment decisions. This work has the potential to change how we classify and treat leukemia by revealing that sex chromosome biology, which has been long overlooked in cancer, plays an active and clinically important role.