Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor
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.
- Publication:
-
Nature
- Pub Date:
- August 1996
- DOI:
- 10.1038/382541a0
- Bibcode:
- 1996Natur.382..541I