Abstract
The B cell lymphomas associated with Epstein-Barr virus (EBV) are not limited to any specific stage of B cell differentiation but covers widely different B cell phenotypes. In vitro infection of the virus negative tumors with a recombinant EBV strain has provided important insights into virus-tumor interaction. Here, we investigated the interaction between EBV and terminally differentiated tumor derived B cells, namely multiple myeloma (MM). The in vitro EBV infected MM expressed restricted viral latency. Acquisition of the virus was accompanied by a partial reprogramming to a mature B cell phenotype. Thus, the plasma cell markers syndecan-1 (CD138), Blimp1 and MUM1 were downregulated, while expression of HLADR, CIITA and TCL1, which are normally not expressed in plasmacytoid cells, was upregulated. The silenced transcription factor gene encoding Pax5 and its target BLNK were activated. Significantly, the free lambda light chains secreted in the medium were reduced in EBV infected MM clones. Collectively, these results suggest that the restricted EBV latency can cause at least partial phenotypic reversion of terminally differentiated B tumor cells. We suggest that the restricted EBV latent gene expression may not only be the consequence but the cause of the mature B cell phenotype, actively participating in the virus persistence.
| Original language | English |
|---|---|
| Pages (from-to) | 165-174 |
| Number of pages | 10 |
| Journal | Cancer Letters |
| Volume | 284 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Nov 1 2009 |
Fingerprint
Keywords
- Differentiation
- EBV
- Latency
- Myeloma
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Epstein-Barr virus infection leads to partial phenotypic reversion of terminally differentiated malignant B cells. / Anastasiadou, Eleni; Vaeth, Signe; Cuomo, Laura; Boccellato, Francesco; Vincenti, Sara; Cirone, Mara; Presutti, Carlo; Junker, Steffen; Winberg, Gösta; Frati, Luigi; Wade, Paul A.; Faggioni, Alberto; Trivedi, Pankaj.
In: Cancer Letters, Vol. 284, No. 2, 01.11.2009, p. 165-174.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Epstein-Barr virus infection leads to partial phenotypic reversion of terminally differentiated malignant B cells
AU - Anastasiadou, Eleni
AU - Vaeth, Signe
AU - Cuomo, Laura
AU - Boccellato, Francesco
AU - Vincenti, Sara
AU - Cirone, Mara
AU - Presutti, Carlo
AU - Junker, Steffen
AU - Winberg, Gösta
AU - Frati, Luigi
AU - Wade, Paul A.
AU - Faggioni, Alberto
AU - Trivedi, Pankaj
PY - 2009/11/1
Y1 - 2009/11/1
N2 - The B cell lymphomas associated with Epstein-Barr virus (EBV) are not limited to any specific stage of B cell differentiation but covers widely different B cell phenotypes. In vitro infection of the virus negative tumors with a recombinant EBV strain has provided important insights into virus-tumor interaction. Here, we investigated the interaction between EBV and terminally differentiated tumor derived B cells, namely multiple myeloma (MM). The in vitro EBV infected MM expressed restricted viral latency. Acquisition of the virus was accompanied by a partial reprogramming to a mature B cell phenotype. Thus, the plasma cell markers syndecan-1 (CD138), Blimp1 and MUM1 were downregulated, while expression of HLADR, CIITA and TCL1, which are normally not expressed in plasmacytoid cells, was upregulated. The silenced transcription factor gene encoding Pax5 and its target BLNK were activated. Significantly, the free lambda light chains secreted in the medium were reduced in EBV infected MM clones. Collectively, these results suggest that the restricted EBV latency can cause at least partial phenotypic reversion of terminally differentiated B tumor cells. We suggest that the restricted EBV latent gene expression may not only be the consequence but the cause of the mature B cell phenotype, actively participating in the virus persistence.
AB - The B cell lymphomas associated with Epstein-Barr virus (EBV) are not limited to any specific stage of B cell differentiation but covers widely different B cell phenotypes. In vitro infection of the virus negative tumors with a recombinant EBV strain has provided important insights into virus-tumor interaction. Here, we investigated the interaction between EBV and terminally differentiated tumor derived B cells, namely multiple myeloma (MM). The in vitro EBV infected MM expressed restricted viral latency. Acquisition of the virus was accompanied by a partial reprogramming to a mature B cell phenotype. Thus, the plasma cell markers syndecan-1 (CD138), Blimp1 and MUM1 were downregulated, while expression of HLADR, CIITA and TCL1, which are normally not expressed in plasmacytoid cells, was upregulated. The silenced transcription factor gene encoding Pax5 and its target BLNK were activated. Significantly, the free lambda light chains secreted in the medium were reduced in EBV infected MM clones. Collectively, these results suggest that the restricted EBV latency can cause at least partial phenotypic reversion of terminally differentiated B tumor cells. We suggest that the restricted EBV latent gene expression may not only be the consequence but the cause of the mature B cell phenotype, actively participating in the virus persistence.
KW - Differentiation
KW - EBV
KW - Latency
KW - Myeloma
UR - http://www.scopus.com/inward/record.url?scp=69549119991&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69549119991&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2009.04.025
DO - 10.1016/j.canlet.2009.04.025
M3 - Article
C2 - 19481340
AN - SCOPUS:69549119991
VL - 284
SP - 165
EP - 174
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 2
ER -