A tumor-initiating cell (TIC) marker was identified and characterized in multiple myeloma (MM) cell lines and patient samples, and evidence suggests that the marker may be a possible therapeutic target. The findings were published online in the Journal of the National Cancer Institute.
The study researchers first investigated possible TIC markers in primary MM samples and identified CD24 as a marker for further evaluation. CD24-positive and CD24-negative multiple myeloma cells were isolated and colony formation capacity was compared, revealing that CD24-positive MM cells had increased capacity for self-renewal, a “key feature” of TICs, according to authors. In addition, CD24-positive MM cells had a more than 2.5-fold higher resistance to treatment compared with CD24-negative MM cells (P <.001).
To evaluate the tumorigenicity of CD24-positive MM cells, 5 mice were injected with 10,000 CD24-positive MM cells and another 5 mice were injected with 10,000 CD24-negative MM cells. All 5 mice injected with CD24-positive MM cells developed a tumor within 39 days of the injection, whereas only 1 of 5 mice injected with CD24-negative MM cells developed a tumor.
To evaluate the clinical relevance of CD24-positive MM cells, primary patient samples were assessed, revealing that the average percentage of CD24-positive MM cells was higher among samples obtained after chemotherapy treatment compared with samples from newly diagnosed patients (8.3% vs 1.0%).
In addition, patients who were newly diagnosed with a higher percentage of CD24-positive MM cells had worse progression-free survival (hazard ratio [HR], 3.81; 95% CI, 5.66-18.34; P <.001) and overall survival (HR, 3.87; 95% CI, 16.61-34.39; P =.002) compared with patients who had a lower percentage of CD24-positive MM cells. In mouse models, the addition of a CD24 antibody to bortezomib resulted in longer survival for mice.
“Our studies demonstrate that CD24+ MM cells maintain the TIC features of self-renewal and drug resistance and provide a target for myeloma therapy,” the study authors wrote in conclusion.
Gao M, Bai H, Jethava Y, et al. Identification and characterization of tumor-initiating cells in multiple myeloma. J Natl Cancer Inst. doi: 10.1093/jnci/djz159