Patients with activated B-cell like diffuse large B-cell lymphoma in high and low infectious disease areas have different inflammatory gene signatures

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with an association with inflammation and viral infections. We hypothesize that environmental factors may be involved in the pathogenesis of DLBCL. In this study, we compared gene expression profiles of lymph node tissues from patients with DLBCL from two different geographical areas with diverse environmental exposures. Specimens from Egyptian and Swedish patients with DLBCL as well as controls were studied. Gene expression analysis using microarray and quantitative polymerase chain reaction demonstrated significantly higher expression of signal transducer and activator of transcription 3 (STAT3) in Swedish as compared to Egyptian patients and control materials from both countries. This was confirmed at protein level using confocal microscopy. The receptor tyrosine kinase ROR1, a “survival factor” for malignant cells, was overexpressed and significantly related to the STAT3 expression pattern. The difference in the expression of genes involved in inflammatory responses and in the tumorigenic process of DLBCL might relate to infectious agents and/or other environmental exposures.

Keywords::

• Diffuse large B-cell lymphoma
• gene expression
• inflammation
• STAT
• viral infections

Acknowledgements

We wish to thank Katalin Benedek at the Karolinska Institutet visualization facility (KIVIF).

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This work was supported by grants from The Swedish Research Council, The Swedish Cancer Foundation, The Cancer Society in Stockholm, The King Gustaf V Jubilee Fund and Torsten and Ragnar Söderberg Foundation and the Swedish International Development Cooperation Agency (SIDA).