Investigation of expression of cancer testis antigens in carfilzomib-resistant multiple myeloma cells

Multiple myeloma (MM) is the second most common hematological cancer that results from the proliferation of abnormal plasma cells producing excessive amounts of one type of antibody in the bone marrow and is characterized by the presence of clinical symptoms of anemia, renal failure, bone destruction, and hypercalcemia. Despite the dramatic improvements in the treatment of MM in recent years, MM is still among the lethal malignancies, as most patients inevitably relapse and become refractory to current therapies. As proteasome inhibition in MM leads to the accumulation of intracellular proteins to cause cell death, the first generation PI, Bortezomib, has revolutionized the survival of MM patients. The second generation PI, Carfilzomib (CFZ), significantly reduces the risk of death by overcoming the resistance in clinically BTZ resistant patients. However, a better understanding of the molecular mechanisms driving malignancy in MM is needed to overcome the resistance to CFZ used in the treatment regimens of relapsed/refractory patients. Cancer/Testicular Antigens (CTAs) are attractive targets for immunotherapy as they are a group of proteins whose expression is limited to the testis under physiological conditions but increased in many types of cancer. It was determined that different CTAs were expressed at different levels in MM cell lines and primary cells obtained from MM patients. In this study, mRNA expression levels of CTA family members MAGE-C1, MAGE-C2, MAGE-A3, COX6B2, KIAA0100, LDH-C4, and SPATA19 were determined for the first time in two different CFZ-resistant MM cell lines using quantitative PCR (qPCR) method. qPCR results show that the mRNA expression levels of the genes involved are significantly reduced in CFZ-resistant cells compared to CFZ-sensitive RPMI 8226 and U266 cells. As a result, it has been seen that the mechanisms that play a role in determining the levels of the relevant CTA proteins in CFZ-resistant MM cells and their stabilization at the post-translational level need to be studied in detail.