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VR09 Cell Line: An EBV-Positive Lymphoblastoid Cell Line with In Vivo Characteristics of Diffuse Large B Cell Lymphoma of Activated B-Cell Type
Authors:Ilaria Nichele  Alberto Zamò  Anna Bertolaso  Francesco Bifari  Martina Tinelli  Marta Franchini  Roberta Stradoni  Fiorenza Aprili  Giovanni Pizzolo  Mauro Krampera
Institution:1. Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, Italy.; 2. Section of Pathological Anatomy, Department of Pathology and Diagnostics, University of Verona, Verona, Italy.; 3. Laboratory of Cytogenetics, Department of Pathology and Diagnostics, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.; University of Navarra, Center for Applied Medical Research, Spain,
Abstract:

Background

small 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 Method

we 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.

Results

VR09 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.

Conclusion

This new EBV-positive cell line may be useful to further characterize in vivo activated DLBCL with plasmacytic features.
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