Remodeling of the bone marrow microenvironment during acute myeloid leukemia progression.

Hematopoiesis requires a complex interplay between the hematopoietic stem and progenitor cells and the cells of the bone marrow microenvironment (BMM). The BMM is heterogeneous, with different regions having distinct cellular, molecular, and metabolic composition and function. Studies have shown that this niche is disrupted in patients with acute myeloid leukemia (AML), which plays a crucial role in disease progression. This review provides a comprehensive overview of the components of vascular and endosteal niches and the molecular mechanisms by which they regulate normal hematopoiesis. We also discuss how these niches are modified in the context of AML, into a disease-promoting niche and how the modified niches in turn regulate AML blast survival and proliferation. We focus on mechanisms of modifications in structural and cellular components of the bone marrow (BM) niche by the AML cells and its impact on leukemic progression and patient outcome. Finally, we also discuss mechanisms by which the altered BM niche protects AML blasts from treatment agents, thereby causing therapy resistance in AML patients. We also summarize ongoing clinical trials that target various BM niche components in the treatment of AML patients. Hence, the BM niche represents a promising target to treat AML and promote normal hematopoiesis.