Today’s myeloma therapy can effectively kill myeloma in many patients and even make them minimal residual disease negative. But then years later, it can grow back. How is this possible?
University of Iowa researchers and colleagues are working to identify which cells are “tumor-initiating” or cause myeloma to grow. In a recent paper, the researchers hypothesize that treatment failures or tumor regrowth are likely due to the persistence of a minor population of tumor initiating cells, which are non-cycling or slowly-cycling and are drug resistant. They believe these cells are CD24 positive by flow cytometry.
Using gene expression profiling, a type of myeloma genetics testing, tumor samples were drawn from 11 myeloma patients. The researchers divided the tumor cells into two groups: side-population cells which contained the tumor initiating cells and main-population cells. Then they analyzed how well these two groups of cells could self-renew and how resistant they were to chemotherapy. Flow cytometry was also used to determine how much CD24 was found on the surface of these cells. Then, the researchers tested anti-CD24 antibodies on myeloma mouse models.
The researchers found that CD24 was highly expressed in the side population cells and that these CD24 positive cells had increased drug resistance, tumor factors and more clonal variation. In fact, only 10 of these CD24 positive cells were needed to create myeloma tumors in 3 out of 5 mice after 27 days.
In patients, the average number of CD24 positive cells in relapsed patients was 8.3% after chemotherapy and for patients in complete remission (but with detectable minimal residual disease). This is compared to 1% of CD24 positive cells in newly diagnosed patients. Myeloma patients with a high percentage of CD24 positive cells had worse progression-free survival and overall survival.
The researchers found success in testing an anti-CD24 monoclonal antibody in the mice. They concluded that these CD24 positive cells help myeloma cells become drug resistant, stay alive and perpetuate myeloma. They are now looking to apply existing anti-CD24 monoclonal antibodies to these targets, adding a new potential myeloma therapy to prevent myeloma regrowth.
This is important research being funded by your donations to the Myeloma Crowd Research Initiative. All (100%) of any donation made to this research goes to the Myeloma Crowd Research Initiative and nothing is taken out for overhead expenses. Please consider a donation for this important program. To date we have raised $164,000 of $500,000 for this and two additional projects and your donations are needed and much appreciated in order to bring this research to the clinic!