CD28, A MARKER ASSOCIATED WITH TUMORAL EXPANSION IN MULTIPLE-MYELOMA

CD28 expression was thoroughly investigated on plasma cells of monoclo nal gammopathy of undetermined significance, multiple myeloma (MM), an d human myeloma cell lines. CD28(+) plasma cells were detected in 19% of 31 monoclonal gammopathy of undetermined significance, 41% of 116 M M, 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 m edullary relapse (P < 0.009), and 14 of 15 (93%) at extramedullary rel apse (P = 0.05), including 10 of 10 (100%) secondary plasma cell leuke mias (P = 0.05). Serial studies in individual patients confirmed the e mergence of CD28(+) myeloma cells with tumoral expansion and treatment failure. This was significantly correlated with the expression of CD2 8 ligand, i.e., CD86 (but not CD80), and with an increase in the proli ferative activity (labeling index) of myeloma cells in bone marrow, Wh ereas the expression of CD56 defines a particular subset of myeloma pa tients, CD28 is the only antigen for which expression correlates with tumor progression. Our data show that an aggressive compartment of CD2 8(+) and CD86(+) myeloma cells emerges during the course of MM in vivo , indicating that CD28 could be aberrantly expressed on highly maligna nt (possibly mutated) myeloma cells. Conversely, a subset of prolifera tive plasmablasts coexpressing CD28 and CD86 could be the normal count erpart of the clonogenic myeloma stem cell because a subset of CD28(+) plasma cells was observed in 6 of 6 cases of reactive plasmocytosis.