Hematopoietic Aging and Leukemia: Mechanistic and Therapeutic Insights

Aging profoundly alters hematopoiesis by impairing stem cell self-renewal, skewing lineage differentiation, and remodeling immune and stromal compartments within the bone marrow. Consequently, these changes contribute to an increased susceptibility to leukemia. Conversely, leukemia contributes to systemic aging. Although the connection between hematopoietic aging and leukemogenesis has been well-recognized, the precise molecular and microenvironmental mechanisms underlying this association remain poorly elucidated. In recent years, emerging studies have identified altered clonal dynamics, chronic inflammation, and niche-dependent metabolic remodeling as major contributors to malignant transformation. Building on these findings, we synthesize current insights into how aging reprograms the hematopoietic ecosystem to promote leukemic initiation and progression, and furthermore, discuss potential strategies to counteract these processes by targeting aging-related pathways.