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Reversal of apoptosis by the leukaemia-associated E2A–HLF chimaeric transcription factor

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Abstract

THE E2A–HLF (for hepatic leukaemia factor) fusion gene, formed by action of the t(17;19) (q22;p13) chromosomal translocation, drives the leukaemic transformation of early B-cell precursors1–4, but the mechanism of this activity remains unknown. Here we report that human leukaemia cells carrying the translocation t(17;19) rapidly died by apoptosis when programmed to express a dominant-negative suppressor of the fusion protein E2A–HLF, indicating that the chimaeric oncoprotein probably affects cell survival rather than cell growth. Moreover, when introduced into murine pro-B lymphocytes, the oncogenic E2A–HLF fusion protein reversed both interleukin-3-dependent and p53-mediated apoptosis. The close homology of the basic region/leucine zipper (bZIP) DNA-binding and dimerization domain of HLF to that of the CES-2 cell-death specification protein of Caenorhabditis elegans5 suggests a model of leukaemogenesis in which E2A–HLF blocks an early step within an evolutionarily conserved cell-death pathway6–9.

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Author notes

  1. Toshiya Inaba

    Present address: Department of Molecular Biology, Jichi Medical School, 311-1 Yakushji, Minamikawachimachi, Tochigi, 329-04, Japan

Authors and Affiliations

  1. Department of Experimental Oncology, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, Tennessee, 38105, USA

    Toshiya Inaba, Takeshi Inukai, Takao Yoshihara, Helga Seyschab, Richard A. Ashmun & A. Thomas Look

  2. Department of Pediatrics, University of Tennessee College of Medicine, 3 N. Dunlap, Memphis, Tennessee, 38163, USA

    A. Thomas Look

  3. The Johns Hopkins Oncology Center, 600 N. Wolfe Street, Baltimore, Maryland, 21287–5001, USA

    Christine E. Canman, Steven J. Laken & Michael B. Kastan

Authors
  1. Toshiya Inaba
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  2. Takeshi Inukai
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  3. Takao Yoshihara
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  4. Helga Seyschab
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  5. Richard A. Ashmun
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  6. Christine E. Canman
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  8. Michael B. Kastan
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  9. A. Thomas Look
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Inaba, T., Inukai, T., Yoshihara, T. et al. Reversal of apoptosis by the leukaemia-associated E2A–HLF chimaeric transcription factor. Nature 382, 541–544 (1996). https://doi.org/10.1038/382541a0

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