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Characterisation and relevance of CD138-negative plasma cells in plasma cell myeloma
Samantha Reid1, S Yang, R Brown
1Medical and Molecular Biosciences, University of Technology, Sydney, NSW, Australia. samantha.reid@uts.edu.au
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 subpopulation 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.
Insights
A subset of plasma cells (PCs) lacking CD138 expression were identified in multiple myeloma patients. These CD138-negative PCs are more immature and proliferate more rapidly, impacting myeloma research and treatment strategies.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- CD138 is commonly used to isolate plasma cells (PCs) in multiple myeloma (MM) research.
- This method may overlook a significant subpopulation of CD138-negative PCs.
Purpose of the Study:
- To investigate the existence and characteristics of CD138-negative PCs in MM patients.
- To highlight the implications of excluding this cell population in MM research.
Main Methods:
- Retrospective analysis of 218 MM patient bone marrow biopsies.
- Flow cytometry used to separate CD138-positive and CD138-negative cell populations.
- Analysis of S-phase fraction to assess proliferation rates.
Main Results:
- A CD138-negative PC population was present in all analyzed MM samples.
- CD138-negative PCs exhibited significantly higher CD45 expression, indicating immaturity.
- CD138-negative PCs showed a significantly higher proliferation rate compared to CD138-positive PCs.
Conclusions:
- CD138-negative PCs are a distinct, more immature, and highly proliferative subpopulation in MM.
- Excluding CD138-negative PCs from analyses may affect gene expression, classification, and drug sensitivity assessments in MM.
- Further research is needed to understand the role of CD138-negative PCs in MM pathogenesis and treatment.
