BioProject

To gain further insights into the role of the transcriptome deregulation in the transition from a normal plasma cell (NPC) to a clonal PC and from an indolent clonal PC to a malignant PC, we performed gene expression profiling in 20 patients with MGUS, 33 with high-risk SMM and 41 with MM. More...

To gain further insights into the role of the transcriptome deregulation in the transition from a normal plasma cell (NPC) to a clonal PC and from an indolent clonal PC to a malignant PC, we performed gene expression profiling in 20 patients with MGUS, 33 with high-risk SMM and 41 with MM. The analysis showed that 126 genes were differentially expressed in MGUS, SMM and MM as compared to NPC. Interestingly, 17 and 9 out of the 126 significant differentially expressed genes were small nucleolar RNA molecules (snoRNA) and zinc finger proteins. GADD45A was the most significant up-regulated gene in clonal PC compared to NPC. Several proapoptotic genes (AKT1 and AKT2) were downregulated and antiapoptotic genes (APAF1 and BCL2L1) were upregulated in MM, both symptomatic and asymptomatic, compared to MGUS. Myc mediated apoptosis signaling is one of the top canonical pathways differentiating the asymptomatic and symptomatic myeloma. When we looked for those genes progressively modulated through the evolving stages of monoclonal gammopathies, eight snoRNA showed a progressive increase while APAF1, VCAN and MEGF9 exhibited a progressive downregulation in the transition from MGUS to SMM and to MM. In conclusion, our data show that although MGUS, SMM and MM are not clearly distinguishable groups according to their GEP, several signaling pathways and genes were significant deregulated in the different steps of transformation process. Overall design: Bone marrow (BM) samples were obtained from 20 patients with MGUS, 33 with high-risk SMM and 41 with MM. All samples corresponded to newly diagnosed untreated patients. To avoid misclassification or overlapping entities we decided to focus on MGUS patients with more than two years of stable follow-up. Samples were classified according to the International Myeloma Working Group criteria. The criteria for defining high-risk SMM has been described previously. In addition, five healthy donors were also included in order to relate the deregulation of gene expression profiling of clonal populations to normal condition. The study was approved by the research ethic committees of all participating centers and written informed consent was obtained from all patients in accordance with the Helsinki Declaration. The main clinical and laboratory characteristics of these patients are shown in Supplementary Table 1. Less...