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ALL

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

Leukemia volume 14, pages 399–402 (2000)Cite this article

Abstract

The pleiotropic transcription factor NF-κB controls cellular apoptotic and growth processes and increasing evidence suggests a role in tumorigenesis. We describe here that constitutively activated NF-κB complexes are found in the vast majority (39 out of 42 samples) of childhood acute lymphoblastic leukemia (ALL) without any subtype restriction. Electrophoretic shift analysis further demonstrates that these complexes are composed of p50-p50 and p65-p50 dimers. Proteasome inhibition in primary ALL cultures results in a hyperphosphorylated form of IκBα, indicating that activation of upstream kinases, which trigger IκBα degradation, has led to nuclear translocation of NF-κB. Careful inhibition of cellular proteolytic activities is of importance when analyzing extracts from primary ALL cells. Degradation of p65 and other proteins in ALL samples could be specifically suppressed by α-1 antitrypsin. Constitutive NF-κB activation is thus a common characteristic of childhood ALL and strongly suggests a critical role of this factor for leukemia cell survival.

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Acknowledgements

We thank U Anderer, Charité Berlin, for pediatric tumor cell lines, R Marschalek, University Erlangen, and T Look, SJCRH, Memphis, TN, for ALL cell lines, KH Seeger, Virchow Klinikum Berlin for ALL samples, respectively, and H Riehm and M Schrappe (chairmen of the ALL-BFM study) for continuous support. R Dettmer kindly provided highly purified, bacterially expressed IκBα.

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  1. Max-Delbrück-Centrum for Molecular Medicine, Universitätsklinikum Charité, Campus Berlin-Buch, Berlin, Germany

    U Kordes, D Krappmann, V Heissmeyer & C Scheidereit

  2. Humboldt University of Berlin, Universitätsklinikum Charité, Campus Berlin-Buch, Berlin, Germany

    WD Ludwig

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  1. U Kordes
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Kordes, U., Krappmann, D., Heissmeyer, V. et al. Transcription factor NF-κB is constitutively activated in acute lymphoblastic leukemia cells. Leukemia 14, 399–402 (2000). https://doi.org/10.1038/sj.leu.2401705

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