Turning the spotlight on bone marrow adipocytes in haematological malignancy and non-malignant conditions

Abstract

Whilst bone marrow adipocytes (BMAd) have long been appreciated by clinical haemato-pathologists, it is only relatively recently, in the face of emerging data, that the adipocytic niche has come under the watchful eye of biologists. There is now mounting evidence to suggest that BMAds are not just a simple structural entity of bone marrow microenvironments but a bona fide driver of physio- and pathophysiological processes relevant to multiple aspects of health and disease. Whilst the truly multifaceted nature of BMAds has only just begun to emerge, paradigms have shifted already for normal, malignant and non-malignant haemopoiesis incorporating a view of adipocyte regulation. Major efforts are ongoing, to delineate the routes by which BMAds participate in health and disease with a final aim of achieving clinical tractability. This review summarises the emerging role of BMAds across the spectrum of normal and pathological haematological conditions with a particular focus on its impact on cancer therapy.

Keywords: adipocytes; haematological malignancies; leukaemia; minimal residual disease; multiple myeloma.

FIGURE 1

Schematic of the healthy BMME. Major tissue participants of BMME involved in blood cell production and HSC homeostasis. BMME, Bone marrow microenvironment; MSC, Mesenchymal stromal cell; HSC, Haematopoietic stem cell; BMAd, Bone Marrow adipocyte.

FIGURE 2

Human and murine adipocytic tissues. (A) Adipocyte tissue distribution in the human body. (B) Dynamics of Bone Marrow Adiposity under during different physiological and pathophysiological contexts. *primarily defined in murine models. BMAd, Bone marrow adipocyte; cBMAd, constitutive bone marrow adipocyte; rBMAd, regulated bone marrow adipocyte; AA, Aplastic anaemia.

FIGURE 3

Types of adipocytes. Summary of the major morphological and functional differences between distinct adipocyte tissue subtypes. *primarily defined in murine models.

FIGURE 4

A Schematic of BM‐MSC differentiation outcomes showing several; positive and negative regulators of BM adipogenesis. BM, Bone marrow; MSC, Mesenchymal stem cell; CTGF, Connective tissue growth factor; GDF‐15, Growth/differentiation factor‐15; wnt, Wingless/Integrated; Sema3A, Semaphorin 3APPARγ, Peroxisome proliferator‐activated receptor gamma; FGF21, Fibroblast factor 21.

FIGURE 5

Summary of the main modes of cross‐talk between BMAd and haematological malignancies. (A) Acute myeloid leukaemia, (B) Acute lymphoblastic leukaemia. AML, Acute myeloid leukaemia; MSCs, Mesenchymal stem cells; BMAd, Bone marrow adipocyte; SDF1α, stromal cell‐derived factor 1 alpha; AML, Acute lymphoblastic leukaemia. (C) Summary of the main modes of cross‐talk between BMAd and Multiple Myeloma. MSCs, Mesenchymal stem cells; BMAd, Bone marrow adipocyte; MM, Multiple myeloma; DKK1, Dickkopf WNT signalling pathway Inhibitor 1; IL‐6, Interleukin 6; MCP‐1, Monocyte chemoattractant protein‐1.