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Updated: Jan 21, 2026
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Identification and Characterization of Tumor-Initiating Cells in Multiple Myeloma
Minjie Gao1,2, Hua Bai1, Yogesh Jethava1
1Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA.
Background:
Treatment failures in cancers, including multiple myeloma (MM), are most likely due to the persistence of a minor population of tumor-initiating cells (TICs), which are noncycling or slowly cycling and very drug resistant.
Methods:
Gene expression profiling and real-time quantitative reverse transcription polymerase chain reaction were employed to define genes differentially expressed between the side-population cells, which contain the TICs, and the main population of MM cells derived from 11 MM patient samples. Self-renewal potential was analyzed by clonogenicity and drug resistance of CD24+ MM cells. Flow cytometry (n = 60) and immunofluorescence (n = 66) were applied on MM patient samples to determine CD24 expression. Therapeutic effects of CD24 antibodies were tested in xenograft MM mouse models containing three to six mice per group.
Results:
CD24 was highly expressed in the side-population cells, and CD24+ MM cells exhibited high expression of induced pluripotent or embryonic stem cell genes. CD24+ MM cells showed increased clonogenicity, drug resistance, and tumorigenicity. Only 10 CD24+ MM cells were required to develop plasmacytomas in mice (n = three of five mice after 27 days). The frequency of CD24+ MM cells was highly variable in primary MM samples, but the average of CD24+ MM cells was 8.3% after chemotherapy and in complete-remission MM samples with persistent minimal residual disease compared with 1.0% CD24+ MM cells in newly diagnosed MM samples (n = 26). MM patients with a high initial percentage of CD24+ MM cells had inferior progression-free survival (hazard ratio [HR] = 3.81, 95% confidence interval [CI] = 5.66 to 18.34, P < .001) and overall survival (HR = 3.87, 95% CI = 16.61 to 34.39, P = .002). A CD24 antibody inhibited MM cell growth and prevented tumor progression in vivo.
Conclusion:
Our studies demonstrate that CD24+ MM cells maintain the TIC features of self-renewal and drug resistance and provide a target for myeloma therapy.
Insights
Persistent multiple myeloma (MM) is linked to drug-resistant tumor-initiating cells (TICs). Targeting CD24+ MM cells, which exhibit TIC properties, offers a promising therapeutic strategy for improving patient outcomes.
Area of Science:
- Hematology
- Cancer Biology
- Immunology
Background:
- Treatment failures in multiple myeloma (MM) are often attributed to drug-resistant tumor-initiating cells (TICs).
- These TICs are characterized by noncycling or slow-cycling behavior, contributing to therapeutic resistance.
Purpose of the Study:
- To identify and characterize the TIC population within multiple myeloma cells.
- To investigate the potential of targeting specific cell surface markers for therapeutic intervention in MM.
Main Methods:
- Gene expression profiling and qRT-PCR were used to compare TIC (side-population) and main MM cell populations.
- Clonogenicity and drug resistance assays assessed self-renewal and resistance of CD24+ MM cells.
- Flow cytometry and immunofluorescence determined CD24 expression in MM patient samples; therapeutic efficacy of CD24 antibodies was evaluated in xenograft models.
Main Results:
- CD24 was highly expressed on MM side-population cells, which also showed high expression of stem cell genes.
- CD24+ MM cells demonstrated increased clonogenicity, drug resistance, and tumorigenicity, with only 10 cells initiating tumors in mice.
- A higher frequency of CD24+ MM cells in patients correlated with inferior progression-free and overall survival, particularly after chemotherapy.
Conclusions:
- CD24+ MM cells possess key tumor-initiating cell characteristics, including self-renewal and drug resistance.
- CD24 represents a viable therapeutic target for overcoming treatment resistance in multiple myeloma.
- Targeting CD24+ MM cells with antibodies shows potential for inhibiting tumor growth and progression.
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