Identification of a Candidate Gene Set Signature for the Risk of Progression in IgM MGUS to Smoldering/Symptomatic <i>Waldenström</i> Macroglobulinemia (WM) by a Comparative Transcriptome Analysis of B Cells and Plasma Cells

• Main Authors: Alessandra Trojani, Barbara Di Camillo, Luca Emanuele Bossi, Livia Leuzzi, Antonino Greco, Alessandra Tedeschi, Anna Maria Frustaci, Marina Deodato, Giulia Zamprogna, Alessandro Beghini, Roberto Cairoli
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Cancers
• Subjects: <i>Waldenström</i> Macroglobulinemia; IgM monoclonal gammopathies of undetermined significance; gene expression profiling; DEGs (differentially expressed genes); KEGG signaling pathways
• Online Access: https://www.mdpi.com/2072-6694/13/8/1837

<i>Waldenström</i> Macroglobulinemia (WM) is a B-cell lymphoma characterized by the precursor condition IgM monoclonal gammopathies of undetermined significance (IgM MGUS). We performed a gene expression profiling study to compare the transcriptome signatures of bone marrow (BM) B-cells and plasma cells of 36 WM patients, 13 IgM MGUS cases, and 7 healthy subjects used as controls (CTRLs) by Affymetrix microarray. We determined 2038 differentially <i>expressed genes</i> (DEGs) in CD19+ cells and 29 DEGs genes in CD138+ cells, respectively. The DEGs identified in B-cells were associated with KEGG pathways, mainly involved in hematopoietic cell lineage antigens, cell adhesion/focal adhesion/transmembrane proteins, adherens junctions, Wnt-signaling pathway, BCR-signaling pathway, calcium signaling pathway, complement/coagulation cascade, platelet activation, cytokine-cytokine receptor interactions, and signaling pathways responsible for cell cycle, apoptosis, proliferation and survival. In conclusion, we showed the deregulation of groups of genes belonging to KEGG pathways in the comparison among WM vs. IgM MGUS vs. CTRLs in B-cells. Interestingly, a small set of genes in B-cells displayed a common transcriptome expression profile between WM and IgM MGUS compared to CTRLs, suggesting its possible role in the risk of transformation of IgM MGUS to WM.