Reframing leukemia-niche interactions: the emerging role of the marrow adipocyte lineage

The bone marrow is a highly dynamic organ that undergoes continuous remodeling to maintain all different hematopoietic cell populations throughout life, adapting during development, aging, and disease. It serves as the primary site of both normal hematopoiesis and leukemic initiation and progression. While mesenchymal stromal cells have received substantial attention for their contribution to support acute leukemia, the bone marrow adipocyte lineage has remained largely overlooked. This has two main reasons: first, adipogenic progenitors are typically grouped under the broad mesenchymal stromal cell umbrella, obscuring the distinct contributions of specific stromal subsets; second, mature bone marrow adipocytes have traditionally been regarded as inert energy reservoirs rather than active components of the marrow microenvironment. Recent evidence challenges this view, demonstrating that different types of adipocyte lineage cells actively promote acute leukemia progression and chemotherapy resistance through distinct mechanisms. In this review, we summarize recent advances in defining subpopulations within the bone marrow adipocyte lineage and outline how leukemic cells exploit their functions. We further discuss how standard chemotherapy may inadvertently reshape leukemic-adipocyte lineage interactions, mediating resistance and facilitating the re-emergence of disease.