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Vav‐1 expression correlates with NFκB activation and CD40‐mediated cell death in diffuse large B‐cell lymphoma cell lines
Author(s) -
Hollmann Annette,
Aloyz Raquel,
Baker Kristi,
Dirnhofer Stephan,
Owens Trevor,
Sladek Robert,
Tzankov Alexandar
Publication year - 2010
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.935
Subject(s) - germinal center , diffuse large b cell lymphoma , cancer research , lymphoma , cd40 , b cell , biology , gene expression profiling , cell , cell culture , gene expression , immunology , antibody , gene , cytotoxic t cell , in vitro , genetics
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.