High frequency of temperature-sensitive mutations of p53 tumor suppressor in acute myeloid leukemia revealed by functional assay in yeast
Jazyk angličtina Země Řecko Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
12792784
Knihovny.cz E-zdroje
- MeSH
- akutní myeloidní leukemie farmakoterapie genetika MeSH
- amifostin farmakologie MeSH
- časové faktory MeSH
- dospělí MeSH
- fungální proteiny metabolismus MeSH
- genetické techniky * MeSH
- geny p53 * MeSH
- imunoblotting MeSH
- kvasinky metabolismus MeSH
- leukocyty metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mutace * MeSH
- mutační analýza DNA MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- plazmidy metabolismus MeSH
- prognóza MeSH
- radioprotektivní látky farmakologie MeSH
- RNA komplementární metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- teplota MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- amifostin MeSH
- fungální proteiny MeSH
- nádorový supresorový protein p53 MeSH
- radioprotektivní látky MeSH
- RNA komplementární MeSH
The tumor suppressor p53 is a transcription factor that participates in control of many cellular functions. All these activities are mediated by direct binding of the p53 tetramer to specific target sequences in promoters of directed genes. Lack of p53 function is often connected with development of cancer, but the frequency of p53 mutations is low in almost all types of leukemia. The aim of this study was to assess the frequency of mutations in the p53 gene in leukocytes of patients with acute myeloid leukemia (AML) using the FASAY functional analysis and to assess the relationship between the presence of p53 mutation and disease outcome. The following observations were made: i) the presence of p53 mutations was detected in 13 of 62 tested AML cases (21%) and in 1 of 4 tested myelodysplastic syndrome (MDS) cases by FASAY; ii) the presence of p53 mutation was shown to be a poor prognostic/predictive factor in AML (p=0.03/0.002); iii) although there is a statistically significant relationship between the presence of p53 mutation and p53 protein accumulation (p=0.05), not all samples having p53 mutation exhibited p53 protein accumulation; iv) five of 13 p53 mutations detected in the leukocytes of AML patients (38.5%) and the mutation detected in the leukocytes of the MDS patient (altogether 6/14-42.9%) were partially inactivating ts mutations. The high frequency of the ts p53 mutations in our study; and a novel modification in performing FASAY, are discussed; v) different ts mutations differ in the level of their temperature sensitivity and in their responsiveness to the cytoprotective drug amifostine.
High frequency of temperature-sensitive mutants of p53 in glioblastoma