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Updated: Jul 18, 2026
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Evidence for cell adhesion-mediated drug resistance of multiple myeloma cells in vivo
R Schmidmaier1, K Mörsdorf, P Baumann
1Department of Hematology and Oncology, Medizinische Klinik Innenstadt, Klinikum der Universität München, München, Germany. ralf.schmidmaier@med.uni-muenchen.de
Background/Aims:
Multiple myeloma is an incurable disease and patients eventually die of disease progression due to drug resistance. VLA-4 (very late antigen 4), VCAM (vascular adhesion molecule), LFA-1 (leukocyte function-associated antigen 1), and ICAM-1 (intercellular adhesion molecule 1)-mediated adhesion of myeloma cells to bone marrow stromal cells induces primary multidrug resistance in vitro. Based on these preclinical data we hypothesized that myeloma cells with strong adhesion - due to strong expression of adhesion molecules on the cell surface - are selected by chemotherapy in patients. To prove this hypothesis we determined the expression levels of adhesion molecules in 31 multiple myeloma patients by flow cytometry.
Methods:
A 3-color stain with CD38, CD138 and antibodies against VLA-4, ICAM-1, LFA-1, and VCAM was performed. The patients were either at diagnosis (chemo-naive; n=17) or at relapse (pre-treated; n=15). Furthermore, the response to the next chemotherapy of chemo-naive patients was correlated with the expression levels of adhesion molecules.
Results:
ICAM-1, VLA-4, and VCAM expression was higher in pre-treated patients than in chemo-naive patients and the expression levels increased with the number of chemotherapy regimens. Primarily multidrug-resistant patients had significantly higher expression levels of VLA-4 and ICAM-1 than responders.
Conclusion:
This study suggests that multiple myeloma cells expressing high levels of VLA-4 and ICAM-1 are drug resistant and that such a subpopulation of cells is selected by chemotherapy.
Insights
Chemotherapy selects for drug-resistant multiple myeloma cells with high expression of very late antigen 4 (VLA-4) and intercellular adhesion molecule 1 (ICAM-1). These adhesion molecules are linked to poorer treatment response in patients.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Multiple myeloma is an incurable blood cancer characterized by eventual drug resistance and disease progression.
- Adhesion molecule-mediated interactions between myeloma cells and bone marrow stromal cells contribute to primary multidrug resistance.
- Preclinical data suggest that chemotherapy may select for myeloma cells with strong adhesion properties.
Purpose of the Study:
- To investigate the hypothesis that chemotherapy selects for multiple myeloma cells with high expression of adhesion molecules.
- To determine the correlation between adhesion molecule expression and drug resistance in multiple myeloma patients.
Main Methods:
- Flow cytometry was used to analyze the expression of VLA-4, ICAM-1, LFA-1, and VCAM on myeloma cells from 31 patients.
- Patients were categorized as either chemo-naive (at diagnosis) or pre-treated (at relapse).
- Adhesion molecule expression was correlated with chemotherapy response in chemo-naive patients.
Main Results:
- Pre-treated patients exhibited higher expression of ICAM-1, VLA-4, and VCAM compared to chemo-naive patients.
- Adhesion molecule expression levels increased with the number of prior chemotherapy regimens.
- Patients with primary multidrug resistance showed significantly higher VLA-4 and ICAM-1 expression than responders.
Conclusions:
- Multiple myeloma cells with high expression of VLA-4 and ICAM-1 are associated with drug resistance.
- Chemotherapy appears to select for a subpopulation of drug-resistant myeloma cells expressing these adhesion molecules.
- Targeting these adhesion molecules may offer new therapeutic strategies for overcoming drug resistance in multiple myeloma.
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