Myeloma and marrow adiposity: Unanswered questions and future directions

Multiple myeloma (MM) is a haematological malignancy characterised by the proliferation and accumulation of terminally differentiated abnormal plasma cells in the bone marrow. Patients suffer from bone pain, factures, anaemia, osteolytic lesions and renal failure. Despite recent advancement in therapy MM remains an incurable disease due to the emergences of drug resistance and frequent relapse. For many decades, research has been heavily focused on understanding the relationship between bone cells such as osteoblast, osteocytes and osteoclasts and the infiltrating tumour cells. However, it is now clear that the tumour-supportive bone microenvironment including cellular and non-cellular components play an important role in driving MM progression and bone disease. One of the most abundant cell types in the bone microenvironment is the bone marrow adipocyte (BMAd). Once thought of as inert space filling cells, they have now been recognised as having specialised functions, signalling in an autocrine, paracrine and endocrine manner to support normal systemic homeostasis. BMAds are both an energy store and a source of secreted adipokines and bioactive substances, MM cells are able to hijack this metabolic machinery to fuel migration, growth and survival. With global obesity on the rise, it has never been more important to further understand the contribution these cells have in both normal and disease settings. The aim of this review is to summarise the large body of emerging evidence supporting the interplay between BMAds and MM cells and to delineate how they fit into the vicious cycle of disease. (c) 2021 Elsevier Ltd. All rights reserved.