A subpopulation of malignant CD34⁺CD138⁺B7-H1⁺ plasma cells is present in multiple myeloma patients

Objective

It is generally assumed that plasma cells from multiple myeloma (MM) patients do not express the stem cell marker CD34. This assumption has led to several clinical trials based on autologous CD34⁺ cell transplantation. However, the results of these trials have been disappointing.

Materials and Methods

We investigated the presence of CD34⁺ cell populations in RPMI 8226, KARPAS 417, and U266 MM cell lines in vitro and during their growth as plasmacytoma tumors in nonobese diabetic severe combined immunodeficient mice, and in plasma cells isolated from the bone marrow of 38 MM patients.

Results

We showed that in both patients and cell lines, a small population of plasma cells expresses CD34. These cells display morphological characteristics of MM plasma cells, are CD19-negative, and express B7-H1 (PD-L1), a T-cell inhibitory molecule. In patients, CD34⁺CD138⁺ cells expressed Ki67, a marker for proliferation. Moreover, when cells from the human myeloma cell line U266 were injected into nonobese diabetic severe combined immunodeficient mice, the U266-derived plasmacytoma tumors showed a large CD34⁺CD138⁺ Ki67⁺ cell population, indicating that these cells were not quiescent in vivo.

Conclusions

MM patients carry a small subpopulation of cycling CD34⁺CD138⁺B7-H1⁺ plasma cells. Their presence may limit the clinical benefits of autologous CD34⁺ cell transplantation.