Origin Of The Malignant Plasma Cell

Myeloma is characterized by proliferation of a monoclonal population of plasma cells. It is a tumor of a postgerminal center, mature B cell that has undergone antigen selection, and somatic hypermutation.151618 However, the origin of the MPC remains controversial.

Molecular studies have cast some insights into the stage of differentiation and the clonal nature of myeloma. Polymerase chain reaction and sequence analysis of the IgVH genes have shown that clonal proliferation occurs in a cell that has undergone somatic hypermutation.15 Consequently, the unique IgH VDJ rearrangement, somatic hypermutation in the CDR regions (in particular, the hypervariable CDR3 region), becomes the signature of the malignant clone. This malignant population is intraclonally homogeneous and stable in spite of disease progression.1619

Phenotypic characterization of myeloma "stem cells" has recently being proposed,20 suggesting they are CD138+ B cells that self-replicate and differentiate into malignant CD138+ plasma cells. These subsets are small (<5%), highly clonogenic, and express CD20+ and surface IgM. They are inhibited by anti-CD20 monoclonal antibody. It was suggested that the therapeutic effect of CD20 antibodies will not be immediate and cannot be measured by standard response criteria, because they target the precursor and not the mature plasma cells that produce the clinical effects.20

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