Publication Title:Int J Cancer. 2009 Jun 15. [Epub ahead of print-PMID: 19530237]. B cell differentiation in EBV-positive Burkitt Lymphoma is impaired at post-transcriptional level by miRNA altered expression. Leucci E, Onnis A, Cocco M, De Falco G, Imperatore F, Antonicelli G, Costanzo V, Cerino G, Mannucci S, Cantisani R, Nyagol J, Mwanda W, Iriso R, Owang M, Schurfeld K, Bellan C, Lazzi S, Leoncini L. Department of Human Pathology and Oncology, University of Siena, Siena Italy.
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 appear 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 BLIMP-1 and the consequent down-regulation of several target genes. Here, we investigated the expression of specific miRNAs predicted to be involved in B cell differentiation and we found that hsa-miR-127 is differentially expressed between EBV-positive and EBV-negative BLs. In particular, it was strongly up-regulated only in EBV-positive BL samples, whereas EBV-negative cases showed levels of expression similar to normal controls, including microdissected GC cells. In addition, we found evidence that hsa-miR-127 is involved in B cell differentiation process through post transcriptional regulation of BLIMP1 and XBP1. The over-expression of this miRNA may thus represent a key event in the lymphomagenesis of EBV positive BL, by blocking the B cell differentiation process.