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The t(8;21) fusion protein, AML1?ETO, specifically represses the transcription of the p14ARF tumor suppressor in acute myeloid leukemia.
- Source :
- Nature Medicine; Jul2002, Vol. 8 Issue 7, p743, 8p
- Publication Year :
- 2002
-
Abstract
- The t(8;21) is one of the most frequent chromosomal translocations associated with acute leukemia. This translocation creates a fusion protein consisting of the acute myeloid leukemia-1 transcription factor and the eight-twenty-one corepressor (AML1?ETO), which represses transcription through AML1 (RUNX1) DNA binding sites and immortalizes hematopoietic progenitor cells. We have identified the p14<superscript>ARF</superscript> tumor suppressor, a mediator of the p53 oncogene checkpoint, as a direct transcriptional target of AML1?ETO. AML1?ETO repressed the p14<superscript>ARF</superscript> promoter and reduced endogenous levels of p14<superscript>ARF</superscript> expression in multiple cell types. In contrast, AML1 stimulated p14<superscript>ARF</superscript> expression and induced phenotypes consistent with cellular senescence. Chromatin immunoprecipitation assays demonstrated that AML1?ETO was specifically bound to the p14<superscript>ARF</superscript> promoter. In acute myeloid leukemia samples containing the t(8;21), levels of p14<superscript>ARF</superscript> mRNA were markedly lower when compared with other acute myeloid leukemias lacking this translocation. Repression of p14<superscript>ARF</superscript> may explain why p53 is not mutated in t(8;21)-containing leukemias and suggests that p14<superscript>ARF</superscript> is an important tumor suppressor in a large number of human leukemias. [ABSTRACT FROM AUTHOR]
- Subjects :
- ACUTE myeloid leukemia
ANEMIA
CANCER
CHROMOSOMAL translocation
ACUTE leukemia
Subjects
Details
- Language :
- English
- ISSN :
- 10788956
- Volume :
- 8
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Nature Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 9511364
- Full Text :
- https://doi.org/10.1038/nm726