Bone Marrow Adipose Tissue: Impacts on Bone Marrow Stem Cell Niche and Hematopoietic System

Bone marrow adipose tissue (BMAT) is a strong orchestrator of the bone marrow microenvironment (BME), bone regeneration and hematopoiesis, but also energy homeostasis and endocrine signaling. Although imposed by its anatomical site, nutritional state or aging, endocrine and metabolic roles of BMAT can overcome BME. The role of BMAT is strongly dependent on marrow and skeletal health, and whether this relationship is causal is still under investigation. Here, we summarized findings indicating an important reprogramming, regulatory and even prognostic role of BMAT in different hematologic malignancies, including myelodysplastic syndrome (MDS), leukemias and multiple myeloma. Bone marrow adipogenesis is an emergency phenomenon that produces hematopoietic stem and progenitor cell (HSPC) niche factors, where accumulation of bone marrow adipocytes (BMAds) may provide selective advantage to specific pre-leukemic HSPCs and clonal hematopoiesis. Lipid status and metabolic changes in BME dictate the outcome of bidirectional crosstalk between BMAds and HSPCs. Lipolysis induced by the presence of leukemic (neoplastic) cells leads to metabolic reprogramming in BMAds, dedifferentiation and potentially to generation of so-called, cancer-associated adipocytes or even fibroblasts. On the other hand, BMAd-released fatty acids, extracellular vesicles, growth factors and lncRNA can trigger survival mechanisms in malignant hematopoietic cells, also modifying their drug response. Collectively, we can assume that revealing of BMAT-associated factors that regulate (neoplastic) hematopoietic process can contribute to the novel strategies for improvement of adult hematological system in aging and malignancy.