Vav-1 expression correlates with NFκB activation and CD40-mediated cell death in diffuse large B-cell lymphoma cell lines.
Hematol Oncol
; 28(3): 142-50, 2010 Sep.
Article
en En
| MEDLINE
| ID: mdl-20155735
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.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
FN-kappa B
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Linfoma de Células B Grandes Difuso
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Antígenos CD40
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Proteínas Proto-Oncogénicas c-vav
Tipo de estudio:
Prognostic_studies
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Hematol Oncol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Canadá