B‐cell differentiation in EBV‐positive Burkitt lymphoma is impaired at posttranscriptional level by miRNA‐altered expression
Author(s) -
Leucci Eleonora,
Onnis Anna,
Cocco Mario,
De Falco Giulia,
Imperatore Francesco,
Giuseppina Antonicelli,
Costanzo Valentina,
Cerino Giovanna,
Mannucci Susanna,
Cantisani Rocco,
Nyagol Joshua,
Mwanda Walter,
Iriso Robert,
Owang Martin,
Schurfeld Karin,
Bellan Cristiana,
Lazzi Stefano,
Leoncini Lorenzo
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24655
Subject(s) - germinal center , biology , b cell , epstein–barr virus , lymphoma , bcl6 , downregulation and upregulation , microrna , cellular differentiation , phenotype , burkitt's lymphoma , antibody , virus , cancer research , virology , immunology , gene , genetics
Abstract 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 BLIMP‐1, 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 BLIMP1 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.