CD138-negative clonogenic cells are plasma cells but not B cells in some multiple myeloma patients

Abstract

Clonogenic multiple myeloma (MM) cells reportedly lacked expression of plasma cell marker CD138. It was also shown that CD19⁺ clonotypic B cells can serve as MM progenitor cells in some patients. However, it is unclear whether CD138-negative clonogenic MM plasma cells are identical to clonotypic CD19⁺ B cells. We found that in vitro MM colony-forming cells were enriched in CD138⁻CD19⁻CD38⁺⁺ plasma cells, while CD19⁺ B cells never formed MM colonies in 16 samples examined in this study. We next used the SCID-rab model, which enables engraftment of human MM in vivo. CD138⁻CD19⁻CD38⁺⁺ plasma cells engrafted in this model rapidly propagated MM in 3 out of 9 cases, while no engraftment of CD19⁺ B cells was detected. In 4 out of 9 cases, CD138⁺ plasma cells propagated MM, although more slowly than CD138⁻ cells. Finally, we transplanted CD19⁺ B cells from 13 MM patients into NOD/SCID IL2Rγc^−/− mice, but MM did not develop. These results suggest that at least in some MM patients CD138-negative clonogenic cells are plasma cells rather than B cells, and that MM plasma cells including CD138⁻ and CD138⁺ cells have the potential to propagate MM clones in vivo in the absence of CD19⁺ B cells.