- Publikační typ
- abstrakt z konference MeSH
AIMS: The aim of this study was to compare the expression profile of selected DNA methyltransferases and global DNA methylation status in patients with different phases of multiple myeloma (MM) . For the analysis, different cellular populations including unsorted myeloma cells and a set of plasma cells purified by relevant antibodies were used. Consequently, laboratory data were compared to patients' clinical data. PATIENTS AND METHODS: For the analysis, unsorted bone marrow cell population of 44 MM patients (30 newly diagnosed, 9 relapsed and 5 patients in remission) and a set of 8 patients' samples of sorted plasma cells were used. We used commercially available RNA isolated from BM of 3 healthy individuals as control samples. Expression analysis of three DNA methyltransferases - DNMT1, DNMT3A, and DNMT3B was performed by quantitative RT-PCR and the patient global DNA methylation profiles were detected by colorimetric assay. RESULTS: Unchanged DNMT1 expression was detected in the selected cohort of patients. Normalized DNMT3A gene expression was globally higher in comparison with controls in unsorted and sorted cell populations. Low (0.08-1.81%) global DNA methylation status in unsorted samples of multiple myeloma patients did not correlate either with expression profiles of monitored DNA methyltransferases or with the stages of MM based on Durie-Salmon and International Staging System. CONCLUSION: This is the first comparative study between DNA methyltransferases expression profiles and global DNA methylation status in different phases of multiple myeloma patients. No significant correlation between the level of global methylation and the clinical stage of the unsorted cell population of patients with multiple myeloma was registered. Overexpression of the DNMT3A gene occurred in both sorted and unsorted cell populations of patients with multiple myeloma. This fact highlights the DNMT3A as a potential marker of multiple myeloma tumor progression. Moreover, we demonstrated comparable results in the expression of DNA methyltransferases in both sorted and unsorted cell populations. This is a promising result from the methodical point of view because when compared to samples of unsorted multiple myeloma cells, samples of sorted cells bring reduction of the number of possible analyses performed.
- MeSH
- DNA methyltransferasa 3A MeSH
- DNA MeSH
- lidé MeSH
- metylace DNA * MeSH
- mnohočetný myelom * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Multiple myeloma (MM) is a still lethal plasma cell malignancy. Epigenetic mechanisms, such as DNA methylation are increasingly recognized as potent modulators of tumor cell survival and drug resistance. However, within the complex approach to the diagnostics, the contribution of DNA methylation has been discovered as important, druggable targets but have not been investigated in MM so far. Therefore, we aim to assess the impact of these modulations for MM pathogenesis and drug resistance. Specifically, we investigate the impact of DNA methylation pattern of prognostically important tumor-suppressor genes for MM. We will focus on the contribution of specific miRNA29 to methylation pattern and function of tumor suppressor genes. We will try to therapeutically modify (5 ́-Aza-2 ́-deoxycytidne) methylation patterns. Experiments will be performed also in a MM tumor-microenvironment model to mirror a possible in vivo relevance. Investigation of the usage of tumor-specific DNA methyltransferases and their possible therapeutic targeting are expected to open new avenues to combat MM.
Mnohočetný myelom (MM) vzniká jako důsledek vícestupňového transformačního procesu plazmatických buněk doprovázený častými genetickými změnami. Biochemické změny, jež jsou podstatou epigenetických procesů, zahrnují metylace DNA a posttranslační modifikace proteinů. Nejvíce studovanou epigenetickou modifikací je metylace DNA, ale v rámci komplexního přístupu v diagnostice a léčbě tohoto onemocnění se zdá být prospěšnější poznání vzájemných interakcí a návazností mezi metylacemi DNA a jinými epigenetickými změnami, jako jsou miRNA nebo metylace histonových proteinů. V našem návrhu bychom se chtěli zaměřit na přínos uvedených změn k hlubšímu pochopení patogeneze onemocnění a také na detekci metylace v důsledku vazby transkripčních faktorů na specifická místa DNA v promotorových oblastech prognosticky významných tumor-supresorových genů u mnohočetného myelomu.
- Klíčová slova
- DNA methylation, hydroxymetylace, hydroxymethylation, mnohočetný myelom, multiple myeloma, metylace DNA, modifikace histonů, Metyltransferazy DNA, miRNA-29, Demetylace DNA, geny TET, DNA methyltransferases, Histone modifications, miRNA-29, Demethylation DNA, TET gene family,
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
Multiple myeloma (MM) is a malignant disease of the plasma cells representing approximately 10% of all hemato-oncological diseases. Detection of the disease is most probable at around 65 years of age, and the average survival of patients is estimated to be 5-10 years, specifically due to frequent relapses and resistance to the therapy used. Thus, the search for new therapeutic approaches is becoming a big challenge. Disulfiram (DSF), a substance primarily known as a medication against alcoholism, has often been mentioned in recent years in relation to cancer treatment for its secondary anti-cancer effects. Recent studies performed on myeloma cell lines confirm high inhibition of the cell growth activity if a complex of disulfiram and copper is used. Its significant potential is now being seen in the cure of haematological malignities.
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Both androgenetic alopecia (AGA) and carcinoma of the prostate (CaP) or benign prostatic hyperplasia (BPH) are androgen-dependent disorders. OBJECTIVE: To investigate the relationships between male androgenetic alopecia, androgen receptor (AR) gene polymorphism (SNP rs6152) and clinical characteristics of BPH and prostate cancer. METHODS: Overall, 309 male subjects with prostate disease (BPH or CaP) were examined. We evaluated the standard grades of AGA (I-VII) by Hamilton-Norwood classification and 195 patients were also assessed by phototrichogram. Prostate-specific antigen (PSA) and testosterone levels were also measured. Polymorphism rs6152 of the AR was evaluated from blood samples by PCR-RFLP. Data were statistically evaluated. RESULTS: The expected positive correlation between age and AGA grade and the expected negative correlation between hair density and age and between anagen/telogen and AGA were found. A statistically significant difference between patients with A and G alleles in terms of AGA grade was found. The predominant G allele was more frequent in patients with higher grade of alopecia and in patients with significantly higher PSA. There was no correlation between diagnosis (BPH or CaP) and polymorphism. Patients with prostate inflammation had a statistically significant higher grade of AGA, together with higher PSA. CONCLUSIONS: We confirmed that the AR gene polymorphism (SNP rs6152 G>A) is associated with the development of AGA and higher PSA levels in patients with BPH but not cancer. A novel finding of our study is that BPH patients with prostate inflammation had a significantly higher grade of AGA together with significantly higher PSA levels.
- MeSH
- alely MeSH
- alopecie krev komplikace genetika MeSH
- androgenní receptory genetika MeSH
- dospělí MeSH
- hyperplazie prostaty krev komplikace genetika MeSH
- jednonukleotidový polymorfismus MeSH
- karcinom krev komplikace genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prostaty krev komplikace genetika MeSH
- prostatický specifický antigen krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- testosteron krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
