Multiple Myeloma and Fatty Acid Metabolism.

Abstract

Multiple myeloma (MM) accounts for 13% to 15% of all blood cancers1 and is characterized by the proliferation of malignant cells within the bone marrow (BM). Despite important advances in treatment, most patients become refractory and relapse with the disease. As MM tumors grow in the BM, they disrupt hematopoiesis, create monoclonal protein spikes in the blood, initiate systemic organ and immune system shutdown,2 and induce painful osteolytic lesions caused by overactive osteoclasts and inhibited osteoblasts.3, 4 MM cells are also extremely dependent on the BM niche, and targeting the BM niche has been clinically transformative for inhibiting the positive-feedback "vicious cycle" between MM cells and osteoclasts that leads to bone resorption and tumor proliferation.5, 6, 7, 8 Bone marrow adipocytes (BMAs) are dynamic, secretory cells that have complex effects on osteoblasts and tumor cells, but their role in modifying the MM cell phenotype is relatively unexplored.9, 10, 11, 12, 13 Given their active endocrine function, capacity for direct cell-cell communication, correlation with aging and obesity (both MM risk factors), potential roles in bone disease, and physical proximity to MM cells, it appears that BMAs support MM cells.14, 15, 16, 17 This supposition is based on research from many laboratories, including our own. Therapeutically targeting the BMA may prove to be equally transformative in the clinic if the pathways through which BMAs affect MM cells can be determined. In this review, we discuss the potential for BMAs to provide free fatty acids to myeloma cells to support their growth and evolution. We highlight certain proteins in MM cells responsible for fatty acid uptake and oxidation and discuss the potential for therapeutically targeting fatty acid metabolism or BMAs from where they may be derived. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.