Abstract

Follicular lymphoma and diffuse large B cell lymphomas comprise the main entities of adult B cell malignancies. Although multiple disease driving gene aberrations have been identified by gene expression and genomic studies, only a few studies focused at the protein level. We applied 2 dimensional gel electrophoresis to compare seven GC B cell non Hodgkin lymphoma (NHL) cell lines with a lymphoblastoid cell line (LCL). An average of 130 spots were at least two folds different in intensity between NHL cell lines and the LCL. We selected approximately 38 protein spots per NHL cell line and linked them to 145 unique spots based on the location in the gel. 34 spots that were found altered in at least three NHL cell lines when compared to LCL, were submitted for LC-MS/MS. This resulted in 28 unique proteins, a substantial proportion of these proteins were involved in cell motility and cell metabolism. Loss of expression of B2M, and gain of expression of PRDX1 and PPIA was confirmed in the cell lines and primary lymphoma tissue. Moreover, inhibition of PPIA with cyclosporine A blocked cell growth of the cell lines, the effect size was associated with the PPIA expression levels. In conclusion, we identified multiple differentially expressed proteins by 2-D proteomics, and showed that some of these proteins might play a role in the pathogenesis of NHL.

Highlights

  • Follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL) compose 60% of nonHodgkin lymphomas (NHLs), both are derived of germinal center or post germinal center B cells[1]

  • Our 2-D gel electrophoresis approach revealed 28 differentially expressed proteins in lymphoma cell lines compared to lymphoblastoid cell line (LCL)

  • For LCLs the transformation mechanism is by Epstein Barr virus (EBV) and its proteins, and should be different from the NHL cell lines

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Summary

Introduction

Follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL) compose 60% of nonHodgkin lymphomas (NHLs), both are derived of germinal center or post germinal center B cells[1]. The resulting expression profiles of 389 proteins were used to compare between the different groups of cell lines. Super SILAC was used to compare cell lysates of 5 GCB and 5 ABC DLBCL cell lines using a heavy stable isotype labelled mixture of cell lines as a reference. This yielded a proteome consisting of 7,500 proteins and a subset of 55 proteins that could differentiate between GCB and ABC DLBCL[10]. Comparison of normal B cells, LPS activated B cells and transgenic Eμ-driven murine B cell lymphoma by 2-D gel electrophoresis revealed 48 differentially expressed proteins[11]

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