Tumor-derived interleukin-1 alpha and leukemia inhibitory factor promote extramedullary hematopoiesis

Extramedullary hematopoiesis (EMH) expands hematopoietic capacity outside of the bone marrow in response to inflammatory conditions, including infections and cancer. Because of its inducible nature, EMH offers a unique opportunity to study the interaction between hematopoietic stem and progenitor cells (HSPCs) and their niche. In cancer patients, the spleen frequently serves as an EMH organ and provides myeloid cells that may worsen pathology. Here, we examined the relationship between HSPCs and their splenic niche in EMH in a mouse breast cancer model. We identify tumor produced IL-1 alpha and leukemia inhibitory factor (LIF) acting on splenic HSPCs and splenic niche cells, respectively. IL-1 alpha induced TNF alpha expression in splenic HSPCs, which then activated splenic niche activity, while LIF induced proliferation of splenic niche cells. IL-1 alpha and LIF display cooperative effects in activating EMH and are both up-regulated in some human cancers. Together, these data expand avenues for developing niche-directed therapies and further exploring EMH accompanying inflammatory pathologies like cancer.