Figure 2.

B-cell differentiation, multiple myeloma (MM) development, and aggressive disease phenotypes. Left panel: pre-B cells migrate from the bone marrow (BM) into the peripheral blood and the germinal center. Memory B-cell differentiation drives the production and localization of plasma cells (PCs) into the BM. Right panel: The earliest clonotypic cell, putatively the MM precursor, can turn into mature premalignant PCs, namely MGUS. Subsequent genetic events lead to overt disease in multiple BM sites. Ultimately, clonal evolution driven by disease biology and BM microenvironment interaction continues to select MM PCs that finally give rise to extramedullary and aberrantly growing sub-clones. EMD: extramedullary disease.