B-cell differentiation in EBV -positive Burkitt lymphoma is impaired at posttranscriptional level by miRNA-altered expression
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Date
2010Author
Leucci, Eleonora
Onnis, Anna
Cocco, Mario
Falco, Giulia De
lmperatore, Francesco
Gluseppina, Antonicelli
Costanzo, Valentina
Cerino, Giovanna
Marinucci, Susanna
Cantisani, Rocco
Nyagol, Joshua
Mwanda, Walter
lriso, Robert
Owang, Martin
Schurfeld, Karin
Bellan, Cristiana
Lazzi, Stefano
Leoncini, Lorenzo
Type
ArticleLanguage
enMetadata
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Endemic, sporadic and HIV-associated Burkitt lymphoma (BL) all have a B-cell phenotype and a MYC translocation, but a variable association with the Epstein-Barr virus (EBV). However, there is still no satisfactory explanation of how EBV participates in the pathogenesis of BL. A recent investigation suggested that EBV-positive and EBV-negative BL have different cells of origin. In particular, according to immunoglobulin gene mutation analysis, EBV-negative BLs may originate from early centroblasts, whereas EBV-positive BLs seem to arise from postgerminal center B cells or memory B cells. The appearance of a germinal center phenotype in EBV-positive cells might thus derive from a block in B-cell differentiation. The exit from the germinal center involves a complex series of events, which require the activation of BLlMP-i, and the consequent downregulation of several target genes. Here, we investigated the expression of specific miRNAs predicted to be involved in B-cell differentiation and found that hsa-miR-127 is differentially expressed between EBV-positive and EBV-negative BLs. In particular, it was strongly upregulated only in EBV-positive BL samples, whereas EBV-negative cases showed levels of expression similar to normal controls, including microdissected germinal centers (GC) cells. In addition, we found evidence that hsa-miR-127 is involved in B-cell differentiation process through posttranscriptional regulation of BLiMPi and XBP1. The overexpression of this miRNA may thus represent a key event in the lymphomagenesis of EBV positive BL, by blocking the B-cell differentiation process.
Citation
International Journal of CancerPublisher
Department of Pathology, Kenyatta National Hospital, University of Nairobi, Nairobi, Kenya
Collections
- Faculty of Health Sciences (FHS) [10377]