New Investigator Research Grant Program

Myeloproliferative neoplasms (MPNs) are a group of blood cancers caused by genetic mutations that lead to the overproduction of blood cells. These mutations trigger a signaling pathway called JAK/STAT, which promotes chronic inflammation, uncontrolled cell growth, and scarring (fibrosis) in the bone marrow. Over time, MPNs can worsen and evolve into a more aggressive form of leukemia with poor outcomes. There is currently a lack of treatments that can stop this dangerous progression. Our research focuses on a natural cleanup process in the body called efferocytosis, where immune cells remove dead or dying cells to reduce inflammation. A key part of this process involves proteins called TAM receptors (Tyro3, Axl, and MERTK) that work with another protein called Gas6. In human MPN patients, we found elevated levels of both soluble MERTK and Gas6 in the blood. These soluble proteins may block the cleanup process, leading to persistent inflammation and bone marrow damage. Using human MPN-related leukemia cell lines, we also found increased MERTK protein. Treatment of the leukemia cell lines with MERTK and Axl inhibitors killed the cells. We believe that the JAK/STAT pathway in MPN interferes with this cleanup system, contributing to disease progression. Our study aims to better understand how this disruption occurs and whether blocking TAM receptors could be a new treatment approach to prevent inflammation and scarring in MPNs to prevent secondary leukemia.