Transcription factor NF-kappa B is constitutively activated in acute lymphoblastic leukemia cells

The pleiotropic transcription factor NF-kappa B controls cellular apoptotic and growth processes and increasing evidence suggests a role in tumorigene sis. We describe here that constitutively activated NF-kappa B complexes ar e found in the vast majority (39 out of 42 samples) of childhood acute lymp hoblastic leukemia (ALL) without any subtype restriction. Electrophoretic s hift analysis further demonstrates that these complexes are composed of p50 -p50 and p65-p50 dimers. Proteasome inhibition in primary ALL cultures resu lts in a hyperphosphorylated form of I kappa B alpha indicating that activa tion of upstream kinases, which trigger I kappa B alpha degradation, has le d to nuclear translocation of NF-kappa B. Careful inhibition of cellular pr oteolytic activities is of importance when analyzing extracts from primary ALL cells. Degradation of p65 and other proteins in ALL samples could be sp ecifically suppressed by alpha-1 antitrypsin. Constitutive NF-kappa B activ ation is thus a common characteristic of childhood ALL and strongly suggest s a critical role of this factor for leukemia cell survival.