CD28, a marker associated with tumoral expansion in multiple myeloma

CD28 expression was thoroughly investigated on plasma cells of monoclonal gammopathy of undetermined significance, multiple myeloma (MM), and human myeloma cell lines. CD28+ plasma cells were detected in 19% of 31 monoclonal gammopathy of undetermined significance, 41% of 116 MM, and 100% of 13 human myeloma cell lines. CD28+ myeloma cells were detected in 21 of 79 (26%) MM cases at diagnosis, 13 of 22 (59%) at medullary relapse (P < 0.009), and 14 of 15 (93%) at extramedullary relapse (P = 0.05), including 10 of 10 (100%) secondary plasma cell leukemias (P = 0.05). Serial studies in individual patients confirmed the emergence of CD28+ myeloma cells with tumoral expansion and treatment failure. This was significantly correlated with the expression of CD28 ligand, i.e., CD86 (but not CD80), and with an increase in the proliferative activity (labeling index) of myeloma cells in bone marrow. Whereas the expression of CD56 defines a particular subset of myeloma patients, CD28 is the only antigen for which expression correlates with tumor progression. Our data show that an aggressive compartment of CD28+ and CD86+ myeloma cells emerges during the course of MM in vivo, indicating that CD28 could be aberrantly expressed on highly malignant (possibly mutated) myeloma cells. Conversely, a subset of proliferative plasmablasts coexpressing CD28 and CD86 could be the normal counterpart of the clonogenic myeloma stem cell because a subset of CD28+ plasma cells was observed in 6 of 6 cases of reactive plasmocytosis.