A study of the NF-κB signalling pathway in human acute myeloid leukaemia.

The transcription factor NF-κB can play both a protective and destructive role in cells. NF-κB protects by signalling for the immune system when cells fall under attack from pathogens. NF-κB signalling becomes a danger to cells when signalling becomes constitutive and can promote excessive inflammation and tumourigenesis. Constitutive NF-κB signalling occurs within acute myeloid leukaemia cells, promoting cell survival. This provides reason to investigate the NF-κB signalling pathway in greater detail. Prevention of NF-κB signalling should lead to cell apoptosis of AML cells but this outcome may be affected by any one of the many signalling components that make up the extremely complex NF-κB signalling pathway. A range of the NF-κB signalling components within AML cells are investigated in detail this study. It was uncovered that although p50 NF-κB levels were consistent in AML and control cell samples, IκB levels were markedly reduced, leading to greater basal NF-κB activity in AML cancer cells compared to control non-cancer cells. Furthermore, this inhibited IκB level observed in AML cells, appeared to be maintained by autocrine TNF production, as anti-TNF treatment impaired the observed response. These findings indicate that IκB levels underlie the high basal NF-κB activity that is observed in AML cancer cells, and possibly other types of NF-κB-dependent cancers. Targetting IκB may help improve cancer chemotherapeutic effectiveness in AML.