Bone Marrow "Yellow" and "Red" Adipocytes: Good or Bad Cells?

Purpose of Review Replacement of red hematopoietic bone marrow with yellow adipocyte-rich marrow constitutes a physiological process associated with aging. Adipocytes have recently emerged as an active part of the bone marrow niche and exert paracrine and endocrine functions, thereby contributing to the regulation of hematopoiesis. Here, we review the current understanding of the interactions between bone marrow adipocytes (BMAs) and hematopoietic cells, as well as their potential role in the progression of hematological malignancies. Recent Findings Until recently, BMAs have been considered space-filler cells. Emerging evidence, however, associates BMA abundance with hematopoietic regulation. On the one hand, human clinical data and experimental findings from animal models suggest that BMAs may act as negative regulators of the hematopoietic microenvironment. On the other hand, recent data has also shown BMAs to exert positive effects on hematopoietic stem cell (HSC) survival. These seemingly contradictory effects could be explained either by a differential effect of distinctBMAsubtypes on hematopoiesis, or by a differential response to BMAstimulation in HSCs versus their committed progeny. Two distinct types of bone marrow adipocytes have previously been described based on anatomical localization. Adipocytes located in the Byellow^ marrow are bigger in size, less responsive to environmental stimuli, and associated with HSC quiescence. On the contrary, adipocytes situated within regions of hematopoietically active Bred^ marrow are significantly more labile and provide important support to regenerating blood populations. Moreover, beyond the presumed differential role of BMA subtypes in hematopoiesis, an imbalanced proportion of stromal constituents could impair their capacity to provide a protective role. Indeed, if BMA commitment has been shown essential for hematopoietic regeneration, skeletal regions constitutively enriched in BMAwould be poorly vascularized, which would in turn negatively affect HSC support. Recently, the interplay of adipocytes and solid cancer has been revealed, with adipocytes promoting the growth of breast, ovarian and prostate cancers. BMAs have been no exception, playing an active role in the support of neoplastic cells in the bone marrow niche, particularly for bone metastatic disease and acute lymphoblastic leukemia (ALL). Acute myeloid leukemia (AML), however, actively suppresses BMAs, which results in impaired myelo-erythroid maturation. Summary It is becoming increasingly evident that BMAs are ideally placed to interact with normal and malignant hematopoiesis. As such, elucidating the relationship between BMAs and specific hematopoietic cell types represents a novel avenue to explore therapeutic strategies for the treatment of hematological malignancies.