Clonogenic MM Progenitor Cells Reside In CD19^-CD38⁺⁺ Plasma Cells

Abstract 1897

For effective treatment of multiple myeloma (MM), it is important to identify clonogenic MM progenitor cells and target them. However, it is still controversial where MM progenitor cells reside. It was reported that CD19⁺ B cells from MM patients generated MM upon transplantation to NOD/SCID mice, while CD19^-CD38⁺⁺ plasma cells generated MM disease in SCID-hu or rab model. In this study, we performed both of those two xenograft models with a series of MM patient samples. To increase engraftment efficiencies, we used highly immuno-deficient NOD/Scid, IL-2Rγnull (NOG) mice as recipients, and cells were injected directly into bone marrow (BM) or intravenously to new born pups. CD19⁺ cells from 10 MM samples were transplanted, but none of them engrafted in NOG mice. Thus, the significance of CD19⁺ B cells was unclear in the MM patients examined in this study. On the other hand, in SCID-rab model, CD19^-CD38⁺⁺ plasma cells, but not CD19⁺ B cells, generate MM disease in 5 out of 13 MM patient samples. In addition, in vitro MM colony-forming cells were highly enriched in CD19^-CD38⁺⁺ plasma cells. Taken together, our results indicate that clonogenic MM progenitors reside in CD19^-CD38⁺⁺ cells and are essential targets to eradicate MM clones.