Waldenström Macroglobulinemia (WM) is a rare type of B-cell lymphoma. It is forerun by an early precursor stage called IgM monoclonal gammopathy of undetermined significance (IgM MGUS). Although previous comparative gene expression studies carried out on B-cells from patients with WM, subjects with IgM MGUS, and healthy subjects (CTRLs) identified several differentially expressed genes, no effective predictors of the risk of progression from IgM MGUS to WM have been yet identified. In this study, we performed a transcriptome comparative gene expression analysis of CD19+ cells and CD138+ cells from 36 WM patients, 13 IgM MGUS subjects and 7 CTRLs to determine differentially expressed genes between the three groups of subjects. We identified 2038 differently significantly expressed genes (DEGs) in B-cells and 29 genes in plasma cells by microarray. The study focused on 115 DEGs in B-cells that are involved in the following KEGG pathways: hematopoietic cell surface antigens, cell adhesion, focal adhesion, transmembrane proteins, adherent junctions, WNT signaling pathway, BCR signaling pathway, calcium signaling pathway, complement cascade and coagulation, platelet activation, cytokine-cytokine receptor interactions and signaling pathways responsible for the cell cycle, apoptosis, cell proliferation and survival. In conclusion, the GEP results identified several deregulated genes and pathways in the comparison among B-cells of WM, IgM MGUS and CTRLs whereas only few deregulated genes came out from the comparison of plasma cells in the three groups. Interestingly, we have noted that the 115 DEGs showed similar expression levels in CTRLs and in IgM MGUS compared to CTRLs, except for 9 genes (HIST1H1B, EZH2, CHEK1, LEF1, ADAM23, RASGRP3, ADRB2, PIK3AP1, CDHR3). This study highlighted a small gene set signature of 9 genes, which have similar expression levels in WM and IgM MGUS compared to CTRLs, suggesting their possible role in the risk of progression of IgM MGUS to WM.
La Macroglobulinemia di Waldenström (WM) è un raro linfoma a cellule B caratterizzato dalla presenza di uno stadio precursore: la gammopatia monoclonale di significato incerto IgM (IgM MGUS). Sebbene studi comparativi di espressione genica condotti su linfociti B di pazienti con WM, soggetti con IgM MGUS e soggetti sani (CTRLs) abbiano identificato numerosi geni differentemente espressi, non sono ancora stati identificati i geni predittivi del rischio di progressione dalla condizione IgM MGUS in WM. In questo studio è stata eseguita un’analisi trascrittomica comparativa di espressione genica delle cellule CD19+ e CD138+ di pazienti WM (n=36), soggetti con IgM MGUS (n=13) e CTRLs (n=7) per determinare i geni differentemente espressi tra i tre gruppi di soggetti. In seguito all’analisi di microarray sono stati identificati 2038 geni differentemente espressi (DEGs) in modo significativo nelle cellule CD19+ e 29 geni nelle cellule CD138+. Lo studio si è focalizzato su 115 DEGs nei linfociti B (CD19+) che sono coinvolti nei seguenti KEGG pathways: antigeni ematopoietici di superficie cellulare, adesione cellulare, adesione focale, proteine transmembrana, giunzioni aderenti, via di segnalazione WNT, via di segnalazione BCR, via di segnalazione del calcio, cascata del complemento e della coagulazione, attivazione piastrinica, interazioni recettore citochina-citochina e vie di segnalazione responsabili del ciclo cellulare, apoptosi, proliferazione e sopravvivenza cellulare. In conclusione, abbiamo identificato numerosi geni e pathways de-regolati nel confronto tra i linfociti B di pazienti con WM, soggetti IgM MGUS e CTRLs, mentre sono stati evidenziati solo pochi geni deregolati dall’analisi delle plasmacellule nei tre gruppi di soggetti. Abbiamo notato che i 115 DEGs avevano un livello di espressione simile nei CTRLs e IgM MGUS rispetto ai WM ad eccezione di 9 geni (HIST1H1B, EZH2, CHEK1, LEF1, ADAM23, RASGRP3, ADRB2, PIK3AP1, CDHR3). Lo studio ha messo in luce una signature molecolare composta dai 9 geni che hanno livelli di espressione simili in WM e IgM MGUS rispetto ai CTRLs, suggerendo il loro possibile ruolo nel rischio di progressione da IgM MGUS a WM.
Un’analisi di microarray di linfociti B e plasmacellule di Gammopatia monoclonale di significato incerto di tipo IgM (IgM MGUS) e Macroglobulinemia di Waldenström (WM) ha identificato una possibile signature molecolare responsabile del rischio di progressione di IgM MGUS in WM
PANZERI, ALESSIA
2020/2021
Abstract
Waldenström Macroglobulinemia (WM) is a rare type of B-cell lymphoma. It is forerun by an early precursor stage called IgM monoclonal gammopathy of undetermined significance (IgM MGUS). Although previous comparative gene expression studies carried out on B-cells from patients with WM, subjects with IgM MGUS, and healthy subjects (CTRLs) identified several differentially expressed genes, no effective predictors of the risk of progression from IgM MGUS to WM have been yet identified. In this study, we performed a transcriptome comparative gene expression analysis of CD19+ cells and CD138+ cells from 36 WM patients, 13 IgM MGUS subjects and 7 CTRLs to determine differentially expressed genes between the three groups of subjects. We identified 2038 differently significantly expressed genes (DEGs) in B-cells and 29 genes in plasma cells by microarray. The study focused on 115 DEGs in B-cells that are involved in the following KEGG pathways: hematopoietic cell surface antigens, cell adhesion, focal adhesion, transmembrane proteins, adherent junctions, WNT signaling pathway, BCR signaling pathway, calcium signaling pathway, complement cascade and coagulation, platelet activation, cytokine-cytokine receptor interactions and signaling pathways responsible for the cell cycle, apoptosis, cell proliferation and survival. In conclusion, the GEP results identified several deregulated genes and pathways in the comparison among B-cells of WM, IgM MGUS and CTRLs whereas only few deregulated genes came out from the comparison of plasma cells in the three groups. Interestingly, we have noted that the 115 DEGs showed similar expression levels in CTRLs and in IgM MGUS compared to CTRLs, except for 9 genes (HIST1H1B, EZH2, CHEK1, LEF1, ADAM23, RASGRP3, ADRB2, PIK3AP1, CDHR3). This study highlighted a small gene set signature of 9 genes, which have similar expression levels in WM and IgM MGUS compared to CTRLs, suggesting their possible role in the risk of progression of IgM MGUS to WM.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/13195