Model of normal B-cell and plasma cell development and MM progression. Myeloma cells develop from aberrant plasma cells. During normal development, precursor B cells undergo VDJ recombination in the bone marrow compartment and migrate to the lymph node where they mature via hypermutation and antigen selection in the germinal center. Post germinal B cells determined to be plasma cells migrate back to the bone marrow. Aberrant plasma cells develop into myeloma cells and are characterized mostly by the primary events of hyperdiploidy of odd-numbered chromosomes or IgH translocations. As myeloma progresses from asymptotic phases (MGUS) to overt disease including plasma cell leukemia, secondary and tertiary genetic aberrations are observed, including del17p (TP53 deletions) and c-Myc translocations.
Semin Oncol. 2016 Dec;43(6):676-681. doi: 10.1053/j.seminoncol.2016.11.004. Epub 2016 Nov 10.