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.
- Inaba, T; Inukai, T; Yoshihara, T; Seyschab, H; Ashmun, RA; Canman, CE; Laken, SJ; Kastan, MB; Look, AT
- August 8, 1996
Volume / Issue
- 382 / 6591
Start / End Page
- 541 - 544
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)