Development of EBV-associated diffuse large B-cell lymphoma in Waldenström macroglobulinemia and mantle cell lymphoma

Varghese, Abraham; Sayala, Hazem A.; Evans, Paul; O’Connor, Sheila J.M.; Patmore, Russell; Hillmen, Peter; Owen, Roger G.

doi:10.1080/10428190802123481

Cited by 12 publications

(6 citation statements)

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“…The establishment of VR09 cell line was likely due to EBV infection; in fact, as EBV was already present in patient’s B cells, we can reasonably assume that the infection drove the transformation into DLBCL once cultured in vitro and injected into mice, thus excluding a culture-dependent contamination by EBV. Indeed, the Association between EBV infection and indolent B-cell neoplasms, such as chronic lymphocytic leukemia, marginal zone lymphoma, lymphoplasmacytic lymphoma has been reported [4], [19], [20] Thus, the positivity of EBV in VR09 cell line is not surprising. Moreover, some studies showed that cases of DLBCL developed from low-grade lymphoproliferative diseases are EBV-positive and that EBV may have a potential role, although not yet completed defined, in the progression of the indolent disease [21], [22].…”

Section: Discussionmentioning

confidence: 99%

VR09 Cell Line: An EBV-Positive Lymphoblastoid Cell Line with In Vivo Characteristics of Diffuse Large B Cell Lymphoma of Activated B-Cell Type

et al. 2012

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Backgroundsmall B-cell neoplasms can show plasmacytic differentiation and may potentially progress to aggressive lymphoma (DLBCL). Epstein-Barr virus (EBV) infection may cause the transformation of malignant cells in vitro.Design and Methodwe established VR09 cell line with plasmacytic differentiation, obtained from a case of atypical, non-CLL B-cell chronic lymphoproliferative disease with plasmacytic features. We used flow cytometry, immunohistochemistry, polymerase chain reaction, cytogenetic analysis and florescence in situ hybridization in the attempt at thoroughly characterizing the cell line. We showed VR09 tumorigenic potential in vivo, leading to the development of activated DLBCL with plasmacytic features.ResultsVR09 cells displayed plasmacytic appearance and grew as spherical tumors when inoculated subcutaneously into immunodeficient Rag2−/− γ-chain−/− mice. VR09 cell line and tumors displayed the phenotype of activated stage of B cell maturation, with secretory differentiation (CD19+ CD20+ CD79a+ CD79b+/− CD138+ cyclin D1- Ki67 80% IgM+ IgD+ MUM1+ MNDA+ CD10- CD22+ CD23+ CD43+ K+, λ- Bcl2+ Bcl6-) and they presented episomal EBV genome, chromosome 12 trisomy, lack of c-MYC rearrangement and Myd88 gene mutation, presence of somatic hypermutation in the VH region, and wild-type p53.ConclusionThis new EBV-positive cell line may be useful to further characterize in vivo activated DLBCL with plasmacytic features.

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Section: Discussionmentioning

confidence: 99%

VR09 Cell Line: An EBV-Positive Lymphoblastoid Cell Line with In Vivo Characteristics of Diffuse Large B Cell Lymphoma of Activated B-Cell Type

et al. 2012

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“…The texture is hard when touched, and the mobility is poor. B-ultrasound in the clinic: mixed echo foci in the subcutaneous muscular layer of the left lower limb, considering as hemangioma [5][6][7].…”

Section: Case Reportmentioning

confidence: 99%

A Case of Extranodal Nk/T Cell Lymphoma Found in Left Leg

2023

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“…WM can transform in approximately 5-10% of patients, and the most common morphological transformation is to aggressive lymphomas like diffuse large B-cell lymphoma (DLBCL) [5,6]. Spontaneous new mutations in the original B-cell clone, mutations secondary to prior therapy with nucleoside analogs (NAs) and infections with Epstein-Barr virus play a role in the transformation to more aggressive histology [7,8]. The 2016 revision of the WHO classification of lymphoid neoplasms includes a new category of high grade B-cell lymphoma that include rearrangements of MYC and BCL2 and/or BCL6, sometimes referred to as 'double-hit' or 'triple hit' lymphomas, respectively [9].…”

Section: Background and Epidemiologymentioning

confidence: 99%

“…• 15-year incidence of transformation: 3.8% EBV appears to play a role in transformation of WM to DLBCL [8] Median survival after histologic transformation 2.7 years [7] PubMed search for transformation of WM to DHL yields 0 results Although one of the six articles listed above (Castillo) notes that poor outcomes in cases of transformed WM may be due to increased expression of BCL-6 and MYC, indicating possible development of DHL [7] The specific genetic changes that underlie these transformation events in the original B-cell clone, remain unknown in WM [5] BCL: B-cell lymphoma; DHL: Double-hit lymphoma; DLBCL: Diffuse large B-cell lymphoma; EBV: Epstein-Barr virus; WM: Waldenström's macroglobulinemia.…”

Section: Case Presentationmentioning

confidence: 99%

Rare Transformation to Double Hit Lymphoma in Waldenstrom’s Macroglobulinemia

et al. 2017

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Waldenström macroglobulinemia (WM) is a lymphoproliferative lymphoma that is characterized by monoclonal immunoglobulin M (IgM) protein and bone marrow infiltration. Its incidence is rare and rarer still is its ability to transform to a B-cell lymphoma, particularly the aggressive diffuse large B-cell lymphoma, which bodes a poor prognosis. When transformation includes mutations of MYC, BCL-2 and/or BCL-6, it is known as a 'double hit' or 'triple hit' lymphoma respectively. This paper presents a rare case of WM with mutations positive for MYC and BCL2, making it a case of double hit B-cell lymphoplasmacytic lymphoma with plasmatic differentiation without morphological transformation to aggressive histology like DLBCL. The paper also broadens to include discussions on current topics in the classification, diagnosis, possible causes of transformation, and treatment of WM, including transformation to double hit lymphoma. The significance of this case lies in that the presence of double hit lymphoma-like genetic mutations in WM have not been previously described in the literature and potentially such changes are harbinger of extra-nodal presentation, aggressive growth, and possibly poor prognosis, if data from other double-hit lymphoma are extrapolated.

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Development of EBV-associated diffuse large B-cell lymphoma in Waldenström macroglobulinemia and mantle cell lymphoma

Cited by 12 publications

References 11 publications

VR09 Cell Line: An EBV-Positive Lymphoblastoid Cell Line with In Vivo Characteristics of Diffuse Large B Cell Lymphoma of Activated B-Cell Type

VR09 Cell Line: An EBV-Positive Lymphoblastoid Cell Line with In Vivo Characteristics of Diffuse Large B Cell Lymphoma of Activated B-Cell Type

A Case of Extranodal Nk/T Cell Lymphoma Found in Left Leg

Rare Transformation to Double Hit Lymphoma in Waldenstrom’s Macroglobulinemia

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