Project 466959

The bone marrows (BM) main job is to produce the blood cells of our immune system in a process called hematopoiesis. In leukemia, the BM becomes filled with cancerous blood cells, which prevents normal hematopoiesis. Healthy BM contains various types of stromal niche cells (the BM soil), including bone marrow resident macrophages (BMΦ), which interact with hematopoietic stem cells (HSC) (the BM seeds) to control HSC growth and retention in the BM. Research in mice has shown that some BMΦ express DARC protein on their cell surface, which binds to CD82 protein expressed on the surface of long-lived HSC, and that this interaction is important for BMΦ regulation of HSC. CD82 is also expressed on leukemic cells, which can sometimes hide within the protective BM niche, helping them to survive standard chemotherapy treatments and leading to disease relapse. While we are starting to understand the CD82-DARC interaction in healthy BM, the CD82-DARC interaction in the leukemic BM niche is still poorly understood. My proposed research will investigate CD82-DARC interactions in leukemia using a cell culture system in which leukemia cells are grown in 3D, surrounded by BMΦ and other supportive niche cells to create an in vitro BM environment that models a true leukemic niche. I will then visualize CD82 and DARC proteins on cultured cells using microscopy. Additionally, I will use leukemic mice models to test whether antibodies that block the CD82-DARC interaction could be used to enhance current chemotherapy drugs. This research would contribute to our understanding of the leukemic BM niche, and aims to identify a new treatment mechanism to improve leukemia therapies and prevent relapse.