Model of metastasis and dissemination in MM. In this schematic figure, the initial site of tumor growth of clonal plasma cells is represented by a solitary plasmacytoma (these are not clinically detected in most cases). In a small group of patients, solitary plasmacytomas do not disseminate. However, in the majority of patients, local invasion occurs, which allows some cells to egress into the peripheral circulation (circulating tumor cells) followed by specific homing into BM niches and local micrometastasis. Micrometastasis is represented by the clinical condition of MGUS. MGUS can progress to macrometastasis or colonization after a long latency period, leading to symptomatic disease with multiple lytic lesions, anemia, hypercalcemia, and renal failure. Genes regulating tumor initiation, metastasis initiation, metastasis progression, and metastasis virulence are represented in the figure. This is not a complete list of genes that could regulate cell trafficking in MM but represents some of the known regulators in cell dissemination and progression in MM.