Transcriptome Analysis of Bone Marrow Plasma Cells in Multiple Myeloma Patients before Treatment

Abstract

Multiple myeloma (MM) is a malignant lymphoproliferative disorder associated with accumulation of terminally differentiated B lymphocytes (plasma cells) in the bone marrow, monoclonal expression of pathologic immunoglobulin, anemia, renal damage, hypercalcemia, and bone lesions. Despite considerable attention to the study of ММ pathogenesis and the development of new drugs, this disease remains incurable. Omics technologies are contributing significantly to the understanding of the molecular mechanisms of plasma cell neoplastic transformation in MM and may lead to the identification of novel therapeutic targets. In this work, the authors performed comparative gene expression analysis in CD138+ cell samples obtained from bone marrow aspirates of 46 MM patients and seven healthy donors using high-throughput RNA sequencing technology. Differential expression analysis identified 1230 genes with statistically significant expression changes in MM patient samples compared to donor samples. Functional analysis of the transcriptome revealed that pathogenetic changes in MM were associated with groups related to growth factors and intracellular signaling (DKK1, BMP4, HGF, TGFB2, FGF), extracellular matrix modification and regulation of cell adhesion (VCAM1, MMP16, LAMP5), ion channel activity (GRIA3, CLCNKA, GABRB2), regulation of immune functions, chromatin organization, cytoskeleton, and Ca²⁺ signaling. A significant proportion of genes from the ion channel category were associated with the regulation of neuronal transmission. The last category is poorly characterized, which could provide a new direction for MM therapy. The presented functional analysis of differentially expressed genes helps to elucidate the molecular mechanisms of MM, which will contribute to the development of new treatment approaches.