The role of epigenetics in the regulation of apoptosis in myelodysplastic syndromes and acute myeloid leukemia. | Aplastic Anemia and MDS International Foundation

The role of epigenetics in the regulation of apoptosis in myelodysplastic syndromes and acute myeloid leukemia.

Journal Title: 
Crit Rev Oncol Hematol
Author(s): 
Karlic H, Herrmann H, Varga F, Thaler R, Reitermaier R, Spitzer S, Ghanim V, Blatt K, Sperr WR, Valent P, Pfeilstöcker M.
Primary Author: 
Karlic H
Original Publication Date: 
Saturday, October 12, 2013

Disordered stem cell epigenetics and apoptosis-regulating mechanisms contribute essentially to the pathogenesis of myelodysplastic syndromes (MDS) and may trigger disease-progression to secondary acute myeloid leukemia (AML). Expression of apoptosis-mediators FAS (CD95) and DAPK1 the latter being also known for its association with autophagy are upregulated in neoplastic cells in patients with low-risk MDS and epigenetically silenced and downregulated in high-risk MDS and AML as confirmed by a study 50 MDS and 30 AMLs complementing this review. 5-Azacytidine (AZA) and 5-aza-2'deoxycytidine (DAC), promoted FAS and DAPK1 gene demethylation and their (re)expression as well as apoptosis in leukemic cell lines (HL-60, KG1) which can be reversed by siRNA against FAS. Thus, promoter-demethylation of FAS and DAPK1 represents a critical mechanism of drug-induced apoptosis in neoplastic cells in MDS and AML which underscores the clinical implication of epigenetically active therapies.

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