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

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

doi:10.3390/cancers13081837

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

Cancers (Basel). 2021 Apr 12;13(8):1837. doi: 10.3390/cancers13081837.

Affiliations

¹ Department of Hematology, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy.
² Department of Information Engineering, University of Padova, 35131 Padova, Italy.
³ Division of Hematology and Bone Marrow Transplant, Cardinale Giovanni Panico Hospital, Tricase, 73030 Lecce, Italy.
⁴ Department of Health Sciences, University of Milan, 20142 Milan, Italy.

Abstract

Waldenström 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 expressed genes (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.

Keywords: DEGs (differentially expressed genes); IgM monoclonal gammopathies of undetermined significance; KEGG signaling pathways; Waldenström Macroglobulinemia; gene expression profiling.