Plasmablastic transformation of a pre-existing plasmacytoma: a possible role for reactivation of Epstein Barr virus infection

Ambrosio, Maria Raffaella; Falco, Giulia De; Gozzetti, Alessandro; Rocca, Bruno Jim; Amato, Teresa; Mourmouras, Vasileios; Gazaneo, Sara; Mundo, Lucia; Candi, Veronica; Piccaluga, Pier Paolo; Cusi, Maria Grazia; Leoncini, Lorenzo; Lazzi, Stefano

doi:10.3324/haematol.2014.111872

Cited by 23 publications

(23 citation statements)

References 14 publications

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“…Furthermore, lytic antigen expression was confirmed by immunohistochemical staining for BMRF1 early lytic protein, a DNA polymerase factor essential for lytic virus replication, observed in 9/13 (70%) of our EBV+ DLBCL cases (Figure ). This was in agreement with similar observations found in other B‐cell lymphomas, where it was proposed that lytically infected B‐cells secrete factors that may promote tumourigenesis, including growth and angiogenesis factors and immunosuppressive cytokines.…”

Section: Resultssupporting

confidence: 56%

“…Consistent with previous results from other studies in B cell malignancies, our findings also suggested a diversity of latency-associated gene expression probably because of noncanonical programs with a subset of cells exhibiting expression of lytic genes. 7,8,11,16,18,19 Furthermore, lytic antigen expression was confirmed by immunohistochemical staining for BMRF1 early lytic protein, a DNA polymerase factor essential for lytic virus replication, 20 observed in 9/13 (70%) of our EBV+ DLBCL cases (Figure 1). This was in agreement with similar observations found in other B-cell lymphomas, 16,19 where it was proposed that lytically infected B-cells secrete factors that may promote tumourigenesis, including growth and angiogenesis factors and immunosuppressive cytokines.…”

Section: Resultsmentioning

confidence: 52%

“…7,8,11,16,18,19 Furthermore, lytic antigen expression was confirmed by immunohistochemical staining for BMRF1 early lytic protein, a DNA polymerase factor essential for lytic virus replication, 20 observed in 9/13 (70%) of our EBV+ DLBCL cases (Figure 1). This was in agreement with similar observations found in other B-cell lymphomas, 16,19 where it was proposed that lytically infected B-cells secrete factors that may promote tumourigenesis, including growth and angiogenesis factors and immunosuppressive cytokines. It has been established that, in a sequential manner, the immediate early genes are activated by cellular transcription factors; then, they activate the promoters of early lytic genes that encode the viral replication proteins.…”

Section: Resultsmentioning

confidence: 52%

“…By this, we are not suggesting that latent and lytic antigens are co‐expressed in the same cell; on the contrary, each cell displayed either the latent antigen or the lytic one, given that the expression of lytic genes is strictly controlled and repressed in the latent phase. This could be one plausible explanation for the positive correlation between their gene expressions as was previously proposed, that lytic cycle allows horizontal spread of EBV increasing the total number of latently infected cells from which transformed cells arise …”

Section: Resultsmentioning

confidence: 95%

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Epstein‐Barr virus lytic cycle involvement in diffuse large B cell lymphoma

Cohen

Vistarop

Huaman³

et al. 2017

Hematological Oncology

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Epstein-Barr virus (EBV)-mediated B cell transformation is achieved predominantly through the action of latent proteins, but recent evidence suggests that lytic EBV replication has also a certain pathogenic role in lymphomagenesis, at least in the early phases of cell transformation. Particularly, in diffuse large B cell lymphoma (DLBCL), the EBV lytic cycle is by and large unexplored, so to disclose lytic cell contribution to lymphomagenesis, our aim was to evaluate viral early and late lytic gene expression in relation to several immune response markers in a series of EBV+ DLBCL from Argentina. An unexpected number of cells expressed lytic transcripts, being transcribed at the BZLF1, BHRF1, and BLLF1 locus, by real-time quantitative polymerase chain reaction. This lytic antigen expression was confirmed by immunohistochemical staining for BMRF1 early lytic protein, and a positive correlation between lytic and latent genes was confirmed, revealing a close link between their expressions in EBV+ DLBCL pathogenesis. Remarkably, BZLF1 displayed a negative correlation with CD4 cell counts, and this could be in part justified by the restriction of antigen presentation previously reported. The direct correlation for the late lytic gene BLLF1 and IFNγ in this series could represent a specific response directed towards this antigen. Interleukin 10 transcripts also displayed a positive correlation with lytic expression, indicating that regulatory mechanisms could be also involved on EBV-associated DLBCL pathogenesis in our series. Complete lytic reactivation in EBV-positive tumours could potentially kill EBV-positive malignant cells, providing a tool to promote tumour cell killing mediated by EBV as a complementary treatment strategy.

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Section: Resultssupporting

confidence: 56%

Section: Resultsmentioning

confidence: 52%

Section: Resultsmentioning

confidence: 52%

Section: Resultsmentioning

confidence: 95%

See 2 more Smart Citations

Epstein‐Barr virus lytic cycle involvement in diffuse large B cell lymphoma

Cohen

Vistarop

Huaman³

et al. 2017

Hematological Oncology

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show abstract

“…Few cases of PBL transformed from another hematological disease have been described, most of these arising from chronic lymphocytic leukemia (CLL) and follicular lymphoma [2], as well as at least two cases described from previous plasmacytomas [3,4]. There are, however, no cases describing transformation from DLBCL.…”

Section: Transformation Of a Previously Diagnosed Diffuse Large B-celmentioning

confidence: 99%