B cell differentiation in EBV-positive Burkitt Lymphoma is impaired at post-transcriptional level by miRNA altered expression

TY - JOUR

T1 - B cell differentiation in EBV-positive Burkitt Lymphoma is impaired at post-transcriptional level by miRNA altered expression

AU - Leucci, E

AU - Onnis, A

AU - Cocco, M

AU - De Falco, G

AU - Imperatore, F

AU - Antonicelli, G

AU - Costanzo, V

AU - Cerino, G

AU - Mannucci, S

AU - Cantisani, R

AU - Nyagol, J

AU - Mwanda, W

AU - Iriso, R

AU - Owang, M

AU - Schurfeld, K

AU - Bellan, C

AU - Lazzi, S

AU - Leoncini, L

PY - 2009

Y1 - 2009

N2 - 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. (c) 2009 UICC.

AB - 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. (c) 2009 UICC.

U2 - 10.1002/ijc.24655

DO - 10.1002/ijc.24655

M3 - Journal article

C2 - 19530237

SN - 0020-7136

JO - Radiation Oncology Investigations

JF - Radiation Oncology Investigations

ER -