This imbalance can be mediated directly by myeloma cells via the receptor activator of NF-B ligand (RANKL), hepatocyte growth factor (HGF) or interleukin (IL)-3, or indirectly via BMSC through the upregulation of RANKL and secretion of IL-6, IL-1β or tumor necrosis factor (TNF)-α [34]. Here, HGF is linked to plasma cell myeloma.