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Vav-1 expression correlates with NFκB activation and CD40-mediated cell death in diffuse large B-cell lymphoma cell lines

✍ Scribed by Annette Hollmann; Raquel Aloyz; Kristi Baker; Stephan Dirnhofer; Trevor Owens; Robert Sladek; Alexandar Tzankov

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
439 KB
Volume
28
Category
Article
ISSN
0278-0232

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✦ Synopsis

Abstract

Diffuse large B‐cell lymphoma (DLBCL) is an aggressive malignancy with a variable response to therapy. We have previously shown that DLBCL cell lines differ in their susceptibility to CD40‐mediated cell death, and that resistance to CD40‐targeted antibodies correlated with increased expression of markers of immature B‐cell and absence of Vav‐1 mRNA. We used gene expression profiling to investigate the mechanism of CD40 resistance in these cell lines, and found that resistance correlated with lack of Vav‐1 and inability to activate NFκB upon CD40 ligation. Analysis of tissue microarrays of 213 DLBCL cases revealed that Vav‐1 expression correlated with a higher proliferative index and the presence of the post‐germinal centre marker Irf‐4. Our results suggest that Vav‐1 expression may be associated with activated B‐cell DLBCL origin and higher proliferative activity, and indicate Vav‐1 as a potential marker to identify tumours likely to respond to CD40‐targeted therapies. Copyright © 2010 John Wiley & Sons, Ltd.

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