CD40 and B chronic lymphocytic leukemia cell response to fludarabine: The influence of NF-kappa B/Rel transcription factors on chemotherapy-induced apoptosis

The levels of tumour necrosis factor receptor (TNF-R) superfamily members c an be altered in lymphoid leukemias, indicating a possible role of such mol ecules in the biology of these neoplasias. In B chronic lymphocytic leukemi a cells, the CD40/CD40L system has been shown to be effective in inhibiting the apoptotic response to fludarabine. The modulation of apoptosis relied on the CD40- induced activity of NF-kappa B/Rel transcription factors. The anti- apoptotic effect of CD40 was abolished using a phosphorothioate kappa B decoy oligodeoxynucleotide. These findings illustrate an example of the biological activity of TNF-R- like molecules in leukemias. They also show t he influence of NF-kappa B/Rel activity on leukemic cell response to apopto genic agents.