The molecular biology of multiple myeloma

Multiple myeloma is an incurable post-germinal center B-cell malignancy. Post-germinal center B cells that have undergone productive somatic hypermutation, antigen selection, and immunoglobulin heavy chain (IgH) switching can generate plasmablasts, which typically migrate to the bone marrow, where the microenvironment enables differentiation into long-lived plasma cells. Based on the current diagnostic criteria proposed by the International Myeloma Working Group, four stages of plasma cell neoplasms can be identified based on the presence of myeloma-defining events. It is thought that karyotypic complexity increases during tumor progression, although karyotypic progression has not been well documented. There is a clear consensus that chromosome content reflects at least two pathways of pathogenesis. Approximately half of tumors are hyperdiploid and typically have multiple trisomies involving chromosomes 3, 5, 7, 9, 11, 15, 19, and 21, but only infrequently have one of the recurrent IgH translocations.