Malignant remodeling of the bone marrow microenvironment in acute myeloid leukemia: mechanisms and therapeutic implications

Abstract

Acute myeloid leukemia (AML) is an aggressive clonal myeloid malignancy characterized by the expansion of differentiation-arrested blasts. Treatment resistance, measurable residual disease, and relapse remain major causes of treatment failure. Experimental and clinical evidence indicates that the bone marrow microenvironment can protect heterogeneous AML-cell populations and can also sustain functionally defined or stem-enriched leukemic stem cell (LSC) populations through partly overlapping but non-identical mechanisms. Under physiological conditions, stromal, vascular, neural, and immune components coordinate hematopoietic stem-cell quiescence, retention, and regeneration. In AML, bulk leukemia cells remodel stromal, vascular, extracellular-matrix, metabolic, and immune compartments, whereas LSC-focused studies specifically implicate niche-dependent homing, quiescence, self-renewal, and persistence. This review therefore distinguishes evidence obtained in bulk AML cells from evidence obtained in functionally defined or stem-enriched LSC populations, compares conserved and disease-specific remodeling programs, and summarizes niche-directed therapeutic strategies.