RRML - Epigenetic changes in myelodysplastic syndrome and acute myeloid leukemia: novel targets for therapy

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Nr. 11(2)/2008

Epigenetic changes in myelodysplastic syndrome and acute myeloid leukemia: novel targets for therapy

Andrei M. Cucuianu, Anca Bacârea, Mariana Paţiu, Delia M. Dima

Abstract:

Epigenetic modifications, defined as DNA changes other than changed nucleotide sequence consist mainly of hypermethylation of gene promoters and histone deacetylation. Through these mechanisms, genes, including tumor suppressor genes can have a functionally altered expression and therefore be “silenced”. Epigenetically silenced tumor suppressor genes are common events in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), usually correlating with poor prognosis. Epigenetic modifications may be useful targets for therapy in MDS and AML. Two groups of drugs, demethylating agents (azacytidine and decitabine) and histone deacetylase inhibitors (phenyl-butyrate, valproic acid and suberoylanilide hydroxamic acid) have recently been proven effective, either alone or in combinations, by several clinical trials in high-risk MDS and elderly high-risk AML. These agents were able to induce responses, even complete responses in patients known to have an extremely poor prognosis. In conclusion, epigenetic changes are important events in MDS and AML pathogenesis and progression; targeting these mechanisms is one of the strategies that have lately been incorporated in the therapeutic armamentarium of high-risk MDS and AML patients.

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Cucuianu AM, Bacârea A, Paţiu M, Dima DM. Epigenetic changes in myelodysplastic syndrome and acute myeloid leukemia: novel targets for therapy. Rev Romana Med Lab. 2008;11(2):39-45