Interleukin-1α and Leukemia Inhibitory Factor Promote Extramedullary Hematopoiesis

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Abstract 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 secondary to solid tumor. We identify an inflammatory gene signature characterized by TNFα expression in HSPCs. We show a role for IL-1α in producing this gene signature and TNFα expression in HSPCs in activating splenic niche activity. We also demonstrate that tumor-derived Leukemia Inhibitory Factor (LIF) induces proliferation of splenic niche cells. IL-1α and LIF display cooperative effects in activating EMH and are both upregulated in some human cancers. Together, these data expand avenues for developing niche-directed therapies and further exploring EMH accompanying inflammatory pathologies like cancer.

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