Year: 2012
Type: article
Abstract: DNA hypermethylation is an important process in oncogenesis, especially in patogenesis of myelodysplastic syndrome (MDS). DNA hypomethylation is associated with inducing reexpression of epigenetically silenced suppressor genes. Two hypomethylating agents are currently used in the treatment of patients with MDS: azacitidine and decitabine. Therapy with those drugs, administered in low doses, results in DNA demethylation through the inhibition of DNA methyltransferase. It is confirmed in randomized trials, that hypomethylating drugs improve outcome of selected patients with MDS. Azacitidine is proved to prolong survival of patients with MDS, and currently is recommended for treatment of patients from the intermediate and high risk group who are not eligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Hypomethylating agents appear to induce leukemic cell differentiation and to increase expression of HLA-DR antigens and other leukemia-associated antigens, which can increase graft versus leukemia effect after allo-HSCT. Detailed mechanism of action of hypomethylating agents is not known. Clinical response is probably related to cellular metabolism of those drugs. Molecular biomarkers should be found to predict therapy responses and patients outcome.
Source: Via Medica Journals
Language: Polish
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2291851245