Novel assay predicts treatment responses in multiple myeloma
A fluorescent assay has been developed that may help predict which patients with multiple myeloma will respond better to certain treatments. The test could be used to detect those multiple myeloma cells that survive chemotherapy and are responsible for disease relapse.
Multiple myeloma, the second most common blood cancer in the United States, is an incurable malignancy involving the white blood cells that normally produce antibodies. As the disease progresses, the multiple myeloma cells accumulate in the bone marrow, causing painful bone lesions and preventing normal blood cell production.
The research team, led by Robert G. Hawley, PhD, of George Washington University in Washington, DC, tested the hypothesis that the tumor-propagating cells in multiple myeloma exhibit stem cell-like properties that confer resistance to the chemotherapeutic agents used to treat patients. The long-term goal of the researchers is to characterize these cancer stem cells so new targeted therapies can be developed.
The researchers used the stem cell imaging dye CDy1 to sort multiple myeloma cells into bright and dim cell populations, and then the cell populations were characterized by RNA-seq deep-sequencing gene expression analysis. One population of the multiple myeloma cells highly expressed the ABCB1 gene, which encodes the P-glycoprotein efflux transporter that is responsible for multidrug resistance. This dim cell population appeared dim because the cells efficiently pumped the dye out.
The investigators found that high levels of ABCB1 confer resistance to the second-in-class drug carfilzomib, which is currently undergoing clinical trials for multiple myeloma. Carfilzomib recently received accelerated FDA approval for the treatment of multiple myeloma patients who have received at least two prior therapies and whose disease continues to worsen.
The next phase of the project will be to translate the laboratory findings to the clinic. Multiple myeloma patients will be screened to determine whether the CDy1 assay can help guide treatment decisions or predict which patients will respond better to carfilzomib.
This study was published in American Journal of Hematology (2013; doi:10.1002/ajh.23387).