Investigation of expression levels of sialyltransferase genes in multiple myeloma cases

Multiple Myeloma (MM), whose incidence is gradually increasing worldwide, is a heterogeneous malignancy characterized by the uncontrolled and clonal proliferation of plasma cells in the bone marrow. It is the second most common hematological cancer after non-Hodgkin lymphoma, which accounts for approximately 1% of all cancers and nearly 10% of hematological malignancies. In recent years, the introduction of novel therapeutic agents has markedly improved treatment outcomes and survival rates. Nevertheless, the heterogeneity of MM, its rapid relapse following initial therapeutic response, and the emergence of treatment resistance render MM a challenging malignancy to manage. Therefore, elucidating the mechanisms underlying the development and progression of MM remains of critical importance. Sialylated structures have attracted attention in the pathogenesis of MM. Abnormal expression of sialic acid on the cell surface confers cancer cells with unique biological properties such as immune evasion, enhanced migration, adhesion, and increased angiogenic potential. Moreover, sialylation has been shown to augment the metastatic capacity of tumor cells and to reduce the efficacy of treatments such as chemotherapy and radiotherapy (Berghuis vd., 2022; Natoni vd., 2019; Schultz vd., 2012). Consequently, investigating the expression levels of sialyltransferase (ST) family genes involved in sialylation is of particular interest. While increased ST expression has been associated with several malignancies, including MM, the specific contribution of individual STs to tumor initiation and progression remains largely unresolved. In this study, bone marrow and peripheral blood samples were collected from newly diagnosed, untreated MM patients, while peripheral blood samples from healthy volunteers served as controls. Following RNA isolation and cDNA synthesis, quantitative real-time polymerase chain reaction (qPCR) was employed to evaluate the expression profiles of selected ST family genes. The genes analyzed were ST3 beta-galactoside alpha-2,3-sialyltransferase 6 (ST3GAL6), ST6 beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1), ST6 alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 1 (ST6GALNAC1) and ST8 alpha-N-acetylneuraminide alpha-2,8-sialyltransferase 1 (ST8SIA1). Since there is no information in the literature regarding potential differences in gene expression between bone marrow and peripheral blood samples in MM patients, we initially compared these two sources. No statistically significant difference was observed for ST3GAL6, ST6GAL1, ST6GALNAC1, or ST8SIA1 expression between bone marrow and peripheral blood samples (p>0.05). However, expression levels of all examined genes were significantly elevated in bone marrow samples of MM patients compared to controls (p<0.05). Similarly, in peripheral blood samples, all genes except ST8SIA1 demonstrated significantly higher expression compared to controls (p<0.05). To the best of our knowledge, this is the first study to report gene expression of ST6GALNAC1 and ST8SIA1 in MM patients, thereby serving as a pioneering reference in this context. By examining the expression levels of selected ST genes, we aimed to elucidate the potential association between MM and sialyltransferase activity. Our findings suggest that ST expression may provide clinically relevant insights into MM pathogenesis. Validation of these results in larger cohorts will be crucial to strengthen the evidence base and clarify the translational implications of STs in MM.