Characterisation and relevance of CD138-negative plasma cells in plasma cell myeloma

Introduction: The use of CD138 to isolate CD138 (+) plasma cells (PCs) from plasma cell myeloma (PCM) patients' bone marrow samples has been used extensively in myeloma research. We sought to highlight the problem with this selection process, by demonstrating that a sub-population of CD138(-) plasma cells exists which is not included in these analyses. Methods: Retrospective analysis of a patient database was carried out on all PCM patient bone marrow biopsies taken between 4/9/07 and 18/2/09 (n = 218). CD138 (+) and CD138(-) cell populations were separated using flow cytometry cell sorter then analyzed for percentage of cells in S phase using plasma cell labeling index as an indicator of proliferation. Results: Database results indicated a CD138(-) PC population in all PCM patient samples which also had a significantly increased (r = 0.53; P < 0.0001) CD45 expression, an indicator or immaturity. Flow cytometric analysis demonstrated the presence of a more immature, higher proliferating CD138(-) PC population through a significantly (t = 3.26; P < 0.02) higher number of CD138(-) PCs in S phase compared with the CD138 (+) cells. Conclusion: We have characterised the CD138(-) PCs as more immature and with a significantly higher proliferative potential. The current trend to ignore this more immature and proliferative subpopulation of malignant PCs may have serious implications when determining gene expression, classifications and drug sensitivity of the malignancy.