Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor.
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.
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- Zinc
- Tumor Suppressor Protein p53
- Tumor Cells, Cultured
- Translocation, Genetic
- Transcription Factors
- Oncogene Proteins, Fusion
- Mutation
- Molecular Sequence Data
- Mice
- Leucine Zippers
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Zinc
- Tumor Suppressor Protein p53
- Tumor Cells, Cultured
- Translocation, Genetic
- Transcription Factors
- Oncogene Proteins, Fusion
- Mutation
- Molecular Sequence Data
- Mice
- Leucine Zippers