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

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.

Plasma proteomic analysis reveals altered protein abundances in HIV‐infected patients with or without non‐Hodgkin lymphoma

“…Over the past decade, researchers using proteomic approaches have provided information on quantitative and qualitative protein patterns in the blood to identify potential cancer biomarkers. 8,9 However, only a minority of published lymphoma proteomic studies have investigated protein expression in patient blood samples, [10][11][12][13][14][15] particularly samples from patients with AIDS-NHL. Xu et al 16 used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to build four models of serum protein fingerprints for identifying potential biomarkers of diffuse large B-cell lymphoma (DLBCL) and distinguishing prognostic markers.…”

Orally bioavailable BTK PROTAC active against wild-type and C481 mutant BTKs in human lymphoma CDX mouse models

“…This stoichiometric alteration might also be determined by neddylation of the Cullin complex, deubiquitinating activities, or other unknown host factors. Hematological cell lines may respond differently to signaling pathways such as NF-κB, BCR-ABL, Janus kinase–signal transducer and activator of transcription, PI3K/Akt/mTOR, and/or MAPK, 48 , 49 which might differentially reprogram cellular networks such as the ubiquitin-proteasome machinery.…”

Anemia ‐ an initial manifestation of Bing‐Neel syndrome: A case report

“…The damage of primary WM to the central nervous system (CNS) mainly includes two reasons. [ 22 ] Hyperviscosity syndrome: a series of clinical manifestations related to cerebral infarction caused by monoclonal IgM protein in the blood. [ 23 ] In rare cases, marked hyperviscosity can lead to loss of consciousness, dementia, disturbance of consciousness, cerebral infarction, and cerebral hemorrhage.…”