Abstract
Survival and maintenance of normal hematopoietic stem cells (HSCs) are regulated by bone marrow (BM) microenvironment. The experimental evidence indicates the vital role of hypoxia in maintenance of the primitive quiescent HSCs within the discrete subendosteal BM niches. Recent findings demonstrate that in the setting of hematologic malignancies BM is highly hypoxic, and that progression of the disease is associated with expansion of hypoxic niches and stabilization of the oncogenic hypoxia-inducible factor-1α (HIF-1α). This chapter will provide an overview of normal and leukemic BM microenvironment with an especial emphasis on pathological hypoxia. We will further describe the development of the hypoxia-activated prodrugs (HAPs) and their applicability in hematological malignancies.
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