Aberrant levels ofSUV39H1andSUV39H2methyltransferase are associated with genomic instability in chronic lymphocytic leukemia
| Autor: | Diêgo Madureira de Oliveira, Antonio R. Lucena-Araujo, Fábio Morato de Oliveira, Juliana Carvalho Alves-Silva, Doralina do Amaral Rabello, Felipe Saldanha-Araujo, Eduardo Magalhães Rego, Martha de Oliveira Bravo, Fabio Pittella-Silva |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genome instability Telomerase Methyltransferase Epidemiology Health Toxicology and Mutagenesis Chronic lymphocytic leukemia Biology medicine.disease Molecular biology Telomere 03 medical and health sciences 030104 developmental biology 0302 clinical medicine hemic and lymphatic diseases 030220 oncology & carcinogenesis Histone methyltransferase Cancer research medicine Telomerase reverse transcriptase Heterochromatin organization neoplasms Genetics (clinical) |
| Zdroj: | Environmental and Molecular Mutagenesis. 58:654-661 |
| ISSN: | 0893-6692 |
| Popis: | Chromosomal alterations are commonly detected in patients with chronic lymphocytic leukemia (CLL) and impact disease pathogenesis, prognosis, and progression. Telomerase expression (hTERT), its activity and the telomere length are other important predictors of survival and multiple outcomes in CLL. SUV39H and SUV420H enzymes are histone methyltransferases (HMTases) involved in several cellular processes, including regulation of telomere length, heterochromatin organization, and genome stability. Here, we investigated whether SUV39H1, SUV39H2, SUV420H1, SUV420H2, and hTERT are associated with genomic instability of CLL. SUV39H (1/2), SUV420H (1/2), and hTERT expression was determined in 59 CLL samples by real time PCR. In addition, ZAP-70 protein expression was evaluated by Flow Cytometry and patients' karyotype was defined by Cytogenetic Analysis. Low expression of SUV39H1 was associated with the acquisition of altered and complex karyotypes. Conversely, high expression of SUV39H2 correlated with cytogenetic abnormalities in CLL patients. The pattern of karyotypic alterations differed in samples with detectable or undetectable hTERT expression. Furthermore, hTERT expression in CLL showed a correlation with transcript levels of SUV39H2, which, in part, can explain the association between SUV39H2 expression and cytogenetic abnormalities. Moreover, SUV39H1 correlated with SUV420H1 expression while SUV420H2 was associated with all other investigated HMTases. Our data show that the differential expression of SUV39H1 and SUV39H2 is associated with genomic instability and that the modulation of these HMTases can be an attractive approach to prevent CLL evolution. Environ. Mol. Mutagen. 58:654-661, 2017. © 2017 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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