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Hematopoietic cells are increasingly recognized as playing key roles in tumor growth and metastatic progression. Although many studies have focused on the functional interaction of hematopoietic cells with tumor cells, few have examined the regulation of hematopoiesis by the hematopoietic stem cell (HSC) niche in the setting of cancer. Hematopoiesis occurs primarily in the bone marrow, and processes including expansion, mobilization, and differentiation of hematopoietic progenitors are tightly regulated by the specialized stem cell niche. Loss of niche components or the ability of stem cells to localize to the stem cell niche relieves HSCs of the restrictions imposed under normal homeostasis. In this review, we discuss how tumor-derived factors and therapeutic interventions disrupt structural and regulatory properties of the stem cell niche, resulting in niche invasion by hematopoietic malignancies, extramedullary hematopoiesis, myeloid skewing by peripheral tissue microenvironments, and lymphopenia. The key regulatory roles played by the bone marrow niche in hematopoiesis has implications for therapy-related toxicity and the successful development of immune-based therapies for cancer. [ABSTRACT FROM AUTHOR]