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

Journal Article (Journal Article)

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 precursors, 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 elegans suggests a model of leukaemogenesis in which E2A-HLF blocks an early step within an evolutionarily conserved cell-death pathway.

Full Text

Duke Authors

Cited Authors

  • Inaba, T; Inukai, T; Yoshihara, T; Seyschab, H; Ashmun, RA; Canman, CE; Laken, SJ; Kastan, MB; Look, AT

Published Date

  • August 8, 1996

Published In

Volume / Issue

  • 382 / 6591

Start / End Page

  • 541 - 544

PubMed ID

  • 8700228

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/382541a0


  • eng

Conference Location

  • England