Adipocytes in hematopoiesis and acute leukemia: friends, enemies, or innocent bystanders?

Abstract

The bone marrow is home to well-balanced normal hematopoiesis, but also the stage of leukemia’s crime. Marrow adipose tissue (MAT) is a unique and versatile component of the bone marrow niche. While the importance of MAT for bone health has long been recognized, its complex role in hematopoiesis has only recently gained attention. In this review article we summarize recent conceptual advances in the field of MAT research and how these developments impact our understanding of MAT regulation of hematopoiesis. Elucidating routes of interaction and regulation between MAT and cells of the hematopoietic system are essential to pinpoint vulnerable processes resulting in malignant transformation. The concept of white adipose tissue contributing to cancer development and progression on the cellular, metabolic, and systemic level is generally accepted. The role of MAT in malignant hematopoiesis, however, is controversial. MAT is very sensitive to changes in the patient’s metabolic status hampering a clear definition of its role in different clinical situations. Here, we discuss future directions for leukemia research in the context of metabolism-induced modifications of MAT and other adipose tissues and how this might impact on leukemia cell survival, proliferation, and antileukemic therapy.

Bone marrow stromal cells from MDS and AML patients show increased adipogenic potential with reduced Delta-like-1 expression

“…Intriguingly, obesity, which also induces inflammation and a plethora of metabolic changes 47 , has been noted as a significant clinical risk factor for the development of AML and MDS 48 , 49 . Although it is not clear from our data whether reduced DLK1 expression in the niche is triggered by AML cells themselves or is a precursor to the development of myeloid malignancy, the association between increased adipogenesis, inflammation and AML warrants further investigation 50 .…”

Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence

“…Taken together, these data demonstrate that adipocyte microenvironments restrict the level of protein synthesis in ALL cells. Such reports are of particular interest because modulating protein synthesis is unique among prior reports of regulatory mechanisms involving adipocyte niches 31 , 37 , 39 , 41 , 42 . Furthermore, this observation directly raises the possibility that adipocyte-mediated cell cycle failure and ALL growth suppression reflect a limitation imposed by low proteome flux 43 .…”

Bone Marrow Homeostasis Is Impaired via JAK/STAT and Glucocorticoid Signaling in Cancer Cachexia Model

“…The bone marrow adipocyte is identified as a negative regulator of normal hematopoiesis [ 62 , 63 ]. An increase in its population inside the bone marrow is associated with certain clinical conditions, including osteoporosis, aging, and obesity, as well as clinical treatments, such as radiation, chemotherapy, and glucocorticoid treatment, all of which accompany myeloid skewing [ 62 , 63 , 64 ]. Therefore, the impaired differentiation balance of the bone marrow MSCs may cause hematopoiesis remodeling at the onset of cancer cachexia following an increase in the bone marrow adipocytes.…”