New overexpressed genes related to cell proliferation stimulation and apoptosis inhibition of plasma cells of multiple myeloma

Abstract

8598 Background: The molecular mechanisms involved in multiple myeloma (MM) are not completely clarified. Serial analysis of gene expression (SAGE) is a powerful tool that allows analysis of overall gene expression pattern. The aim of this study was identified the global gene expression in malignant plasma cells (MPC) of MM. Methods: MPC were obtained from bone marrow (BM) of MM IgG patients using the CD138-antibody in a magnetic column. Normal plasma cells (NPC) were obtained by differentiation of BM B cells from a healthy individual. Libraries were performed with I-SAGE kit and were compared. To investigate the reliability of the MPC profile, 16 genes were studied by quantitative real-time polymerase chain reaction (qPCR) in the sample used to generate the library and in other 13 MM IgG patients’ samples. Results: A total of 84 965 tags from MPC SAGE and 77 080 tags from NPC SAGE profiles were generated, representing 24 601 and 25 527 unique tags, respectively. In comparison of the unique tags, 476 tags were found differentially-expressed at significant levels (fold≥ 5; P< 0.01). qPCR confirmed the gene expression measured by SAGE in 14 out of 16 (87.5%) analyzed genes. The genes differentially-expressed were clustered to their main function evidencing a cluster of overexpressed genes in MPC, related to cell proliferation and differentiation (FOSB, DUSP1, LATS2), apoptosis inhibition (IER3, TEGT, MCL1), proteasome-ubiquitines, chemokine and chemokine receptor (RGS2, CCL5, S100A9, S100A4), and transcriptional and translational process (CFOS, CJUN, EGR1, RHOB). In contrast, MPC underexpressed cell signaling (TCL1A), B cell differentiation (CD19, CD40), cytokine and cytokine receptor production (FCER2, IL6-ST), chemokine production (CCL17, CCL2), transcriptional process (PRDM2, RNAse1), and apoptosis stimulation (BMF, GSR). SAGE permitted the detection of genes involved in the stimulation of cell proliferation (LATS2, S100A4, S100A9, EGR1, RHOB) and the apoptosis inhibition (BMF, GSR), not previously described in MM, and also unknown sequences, which probably constitute novel genes. Conclusions: These findings contribute to clarify the MM pathology, as well as to highlight specific targets for new therapies. Financial support: FAPESP No significant financial relationships to disclose.