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Medical Tribune | March 25th, 2014 | Category: Workbook C | Page: 19 | Author: Mgr. Nikola Čuřík, Ph. D., Mgr. Martina Dluhošová | Topic: 1st Medical Faculty of Vidaza (azacytidine) in the Czech Republic has been using for almost two years as first-line treatment for patients with myelodysplastic syndrome (MDS) at a higher risk of disease (high and very high risk by IPSS-R) and in patients with acute myeloid leukemia (AML). Azacytidine synthesized in the mid 60s Czechoslovak scientists of Sciences (whistling et al., 1964), that for him - as an analogue of one of the bases of DNA - tested the potential cytostatic effect and its potential use in the therapy of malignant diseases. This time, however, due to the identified negative effects of azacytidine occurred. It is currently being changed, but despite promising effect azacytidine in hematological malignancies is its molecular action completely clarified. Just published work (Dluhošová et al., 2014), from laboratories 1 Faculty of Medicine moves knowledge of azacytidine step further. Azacytidine in MDS clinical practice at the center of the scientists and doctors azacytidine back in the 80s and 90s, when it began to examine its ability to induce the low concentrations of cellular DNA demethylation. This property is used in the treatment of patients with MDS and some groups of patients with AML, which was described aberrantly increased DNA methylation in tumor cells. Clinical studies have shown that treatment with azacytidine leads to prolongation of overall survival of patients treated. In clinical randomized trial AZA-001 Phase III 358 patients with higher risk MDS and AML achieve the overall survival rate after two years at azacytidine treatment 50.8% of patients compared with 26.2% of patients enrolled in the conventional regimens (Fenaux et al ., 2009). At 113 AML patients included in this study, two years in the treatment with azacytidine survived 50% of patients compared with 16% of patients treated conventionally (Fenaux et al., 2010). The ongoing phase III trial AZA-AML-001 to 480 patients with primary and secondary AML aims to verify these results. Good results azacytidinová therapy in patients with MDS and AML as well as in the Czech Republic. Of 92 evaluable patients st foy la grande with MDS at higher risk, respectively. with AML (including 28 patients with AML <30% blasts and 7 patients st foy la grande with AML> 30% blasts) st foy la grande treated between October 2008 and June 2012 in the Czech Republic, they reached 67.8% overall survival at one year, with a median total length life of 16.4 months (Jonášová et al., 2013). Positive results azacytidine in clinical st foy la grande practice in patients with MDS or AML, leading to its growing use as a promising therapeutics such malignancies. st foy la grande Despite these achievements, however, when therapy st foy la grande with azacytidine, many challenges remain, in particular the fact that many patients with MDS do not correspond to azacytidine and other patients eventually erupts resistance to its effects. Patients with MDS who experience treatment failure azacytidine, tend to have a poor prognosis with a median overall survival of 5.6 months and fifteen percent probability of survival of two years (Prébet et al., 2011). Even worse prognosis after treatment failure with azacytidine, patients with AML. For these reasons, continued intensive research aimed at understanding the molecular and cellular mechanisms of action azacytidine that these significant differences in the responses of individual st foy la grande patients with MDS and AML explained. Epigenetics - mechanisms to control transcription of DNA - for MDS MDS is a group of clonal bone marrow disease with renal cell differentiation and frequent progression to AML. The disease is characterized st foy la grande by high variability in its clinical expression. As with many other clonal malignancy occurs even in cells of patients