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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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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DOI: https://doi.org/10.1038/382541a0
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