Upregulation of CD24 inhibits the clearance of senescent JAK2V617F neutrophils, which interact with megakaryocytes to induce a myelofibrosis and an osteosclerosis. (A-B) JAK2V617F neutrophils express low levels of CD24 at baseline (A), but JAK2V617F increases GM-CSF levels, which, in turn, upregulates CD24 (B). (B) These increased levels of CD24 inhibit the process of efferocytosis by macrophages and thereby the clearance of senescent neutrophils that accumulate in JAK2V617F MPN. (C) These senescent neutrophils interact with megakaryocytes through the binding of CD24 on P-selectin located on demarcation membranes (emperipolesis). This interaction activates TGF-β1 through enzymes such as myeloperoxidase, which induces bone marrow fibrosis and osteosclerosis by activating myofibroblasts and osteoblasts. (D) Anti-CD24 blocking antibodies reverse the process.