Pickering, B.M., De Mel, S., Lee, M., Howell, M., Habens, F., Dallman, C.L., Neville, L.A., Potter, K.N., Mann, J., Mann, D.A., Johnson, P.W.M., Stevenson, F.K. and Packham, G. (2007) Pharmacological inhibitors of NF-kappa B accelerate apoptosis in chronic lymphocytic leukaemia cells. Oncogene, 26 (8), 1166-1177. (doi:10.1038/sj.onc.1209897).
Abstract
Nuclear factor-kappaB NF-kappa B) is a transcription factor that plays a critical role in the inappropriate survival of various types of malignant cells. Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy in the Western world. Although overexpression and regulation of NF-kappa B has been described in CLL, its function remains unclear. Exposure of CLL cells to BAY117082 or Kamebakaurin, potent pharmacological inhibitors of the NF-kappa B pathway, accelerated apoptosis in approximately 70% of cases. Sensitivity to NF-kappa B pathway inhibitors was not related to the prognostic markers VH status, CD38 or Zap70 expression, or to the levels of nuclear NF-kappa B. Normal peripheral B cells were resistant to the apoptosis-inducing effects of these compounds. Cell death induced by the inhibitors was associated with activation of caspase-9 and -3, and loss of mitochondrial membrane polarization, but did not involve changes in the expression of Bcl-2 or Mcl-1. Inhibitors caused an increase in c-jun NH2-terminal kinase activity in CLL, but this did not appear to be important for apoptosis. Microarray analysis identified some potential novel NF-kappa B target genes, including interleukin-16- and the Bcl-2- related survival protein Bcl-w. These results demonstrate that a substantial proportion of CLL are dependent on NF-kappa B for enhanced survival and suggest that inhibition of NF-kappa B may have therapeutic potential.
This record has no associated files available for download.
More information
Identifiers
Catalogue record
Export record
Altmetrics
Contributors
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.