| Abstract [eng] |
Leukemia is a blood cancer caused by genetic alterations in hematopoietic cells. In this study, we concentrated on myeloid leukemia, which is a very heterogeneous disease. Its treatments is usually challenging, thus the development of new therapy approaches is necessary. The aim of our study ‒ to elucidate molecular mechanisms in human myeloid leukemia cells using epigenetic and metabolic regulators. We demonstrated that natural polyphenol EGCG causes anti-cancerous epigenetic changes in acute promyelocytic leukemia cells and induces cellular senescence in acute promyelocytic leukemia and chronic myeloid leukemia cells in vitro. EHMT2/G9A histone methyltransferase synthetic inhibitor BIX-01294 causes anti-cancerous down-regulation of various epigenetic regulators in acute promyelocytic leukemia and chronic myeloid leukemia cells in vitro. Also, we showed that histone methyltransferase inhibitor 3-deazaneplanocin A and histone deacetylase inhibitor belinostat enhance conventional treatment for acute promyelocytic leukemia in vitro and ex vivo. Moreover, we demonstrated that oxidative phosphorylation inhibitor metformin modulates expression levels of proteins taking part in metabolic pathways of therapy-resistant acute myeloid leukemia patients’ cells ex vivo, which might be useful in combinations with other therapeutics. |
