A study led by Robert G. Hawley, Ph.D., professor and chair of the department of anatomy and regenerative biology at the George Washington University (GW) School of Medicine and Health Sciences (SMHS), may help predict which patients with multiple myeloma will respond better to certain treatments. The study, titled "Identification of an ABCB1 (P-glycoprotein)-positive carfilzomib-resistant myeloma subpopulation by the pluripotent stem cell fluorescent dye CDy1," was published in the American Journal of Hematology and is available online at: http://bit.ly/VWDIgT.
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.
"Our hope is that the fluorescent assay we have developed will help physicians monitor the newest treatment option for multiple myeloma patients and determine how well it is working," said Hawley.
Hawley and his team of researchers reported a test that could be used to detect the multiple myeloma cells that survive chemotherapy and are responsible for disease relapse (referred to as tumor-propagating cells).
The researchers 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 the patients. The team's long-term goal is to characterize these so-called 'cancer stem cells' in order to develop new targeted therapies that will eradicate the cells and cure the disease. As a first step toward this goal, the research team used a new stem cell imaging dye CDy1, and they isolated pure populations of CDy1-bright and CDy1-dim cells from multiple myeloma cell lines by fluorescence-activated cell sorting (a specialized application of flow cytometry). These multiple myeloma populations were then characterized using RNA-seq 'deep-sequencing' gene expression analysis. Through this next-generation genomics approach, the researchers demonstrated that the CDy1-bright cells did indeed exhibit increased expression of many genes associated with stem cell activity. However, they also noted that the ABCB1 gene, which encodes the P-glycoprotein efflux transporter responsible for multi-drug resistance, was highly expressed in the CDy1-dim population. In functional studies, the investigators determined that dim CDy1 staining was due to the fact that the dye was being efficiently pumped out of the cells by the ABCB1 transporter.