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Molecular Cytogenetics and Cytogenetics

The leukemogenic transcription factor E2a-Pbx1 induces expression of the putative N-myc and p53 target gene NDRG1 in Ba/F3 cells

Leukemia volume 15, pages 362–370 (2001)Cite this article

Abstract

The chimeric transcription factor E2a-Pbx1 is expressed as a result of the 1;19 chromosomal translocation in some 5% of cases of pediatric acute lymphoblastic leukemia. We investigated the biological and transcriptional consequences of forced expression of E2a-Pbx1 in the interleukin-3 (IL-3) dependent, bone marrow-derived cell line Ba/F3. We show that forced expression of E2a-Pbx1 induces apoptosis in Ba/F3 cells without apparent effects on cell cycle progression. This pro-apoptotic effect is enhanced on cytokine deprivation. Furthermore, using cDNA representational difference analysis (RDA), we show that these cellular effects are associated with marked induction of the gene NDRG1, which was previously identified as a target of transcriptional repression by N-myc and induction by the tumor suppressor protein p53. We identify a portion of the NDRG1 promoter capable of mediating transcriptional induction by E2a-Pbx1 and show that NDRG1 is also induced on simple IL-3 deprivation of BaF3 cells. Although we show that E2a-Pbx1 induction of NDRG1 is not impaired as a result of targeting p53 using HPV E6, and therefore does not appear to be p53-dependent, our results overall are consistent with the notion that induction of NDRG1 by E2a-Pbx1 may represent part of an apoptotic or cytostatic cellular response to oncogene activation.

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Acknowledgements

We thank Drs Gerald Krystal, Frank Rauscher, Gary Nolan and Gordon Peters for providing reagents, as indicated in the text, and Dr Stephen Hunger for providing WEHI-3B cells and helpful comments on the manuscript. This work was supported by operating grants from The Hospital for Sick Children Foundation and The National Cancer Institute of Canada.

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Authors and Affiliations

  1. Department of Pathology, Queen's University, Kingston, K7L 3N6, Ontario, Canada

    MN Rutherford, GRL Bayly, BP Matthews & DP LeBrun

  2. Institute for Molecular and Cellular Biology, Osaka University, Osaka, Japan

    T Okuda & H Kondoh

  3. Department of Pathology, Erasmus University Rotterdam, Rotterdam, The Netherlands

    WMN Dinjens

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  1. MN Rutherford
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Rutherford, M., Bayly, G., Matthews, B. et al. The leukemogenic transcription factor E2a-Pbx1 induces expression of the putative N-myc and p53 target gene NDRG1 in Ba/F3 cells. Leukemia 15, 362–370 (2001). https://doi.org/10.1038/sj.leu.2402059

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