Inhibitors of histone deacetylase relieve ETO-mediated repression and induce differentiation of AML1-ETO leukemia cells
| Autor: | J, Wang, Y, Saunthararajah, R L, Redner, J M, Liu |
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| Rok vydání: | 1999 |
| Předmět: |
Transcription
Genetic Chromosomes Human Pair 21 Recombinant Fusion Proteins Apoptosis Cell Differentiation 3T3 Cells Hydroxamic Acids Phenylbutyrates Translocation Genetic Neoplasm Proteins DNA-Binding Proteins Histone Deacetylase Inhibitors Mice RUNX1 Translocation Partner 1 Protein Leukemia Myeloid Proto-Oncogene Proteins Acute Disease Core Binding Factor Alpha 2 Subunit Tumor Cells Cultured Animals Humans Enzyme Inhibitors Chromosomes Human Pair 8 Transcription Factors |
| Zdroj: | Cancer research. 59(12) |
| ISSN: | 0008-5472 |
| Popis: | The (8;21) translocation, found in 12% of acute myeloid leukemia (AML), creates the chimeric fusion product, AML1-ETO. Previously, we demonstrated that the ETO moiety recruits a transcription repression complex that includes the histone deacetylase (HDAC1) enzyme. Here, we used inhibitors of HDAC1 to study the pathophysiology of AML1-ETO. Both the potent inhibitor, trichostatin (TSA), and the well-known but less specific inhibitor, phenylbutyrate (PB), could partially reverse ETO-mediated transcriptional repression. PB was also able to induce partial differentiation of the AML1-ETO cell line, Kasumi-1. With the intention of developing a clinically useful protocol, we combined PB with a number of other agents that induced differentiation and apoptosis of Kasumi-1 cells. In summary, transcriptional repression mediated by AML1-ETO appears to play a mechanistic role in the t(8;21) AML, and relief of repression using agents such as PB (alone or in combination) may prove to be therapeutically useful. |
| Databáze: | OpenAIRE |
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