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

Abstract 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...

Full description

Saved in:
Bibliographic Details
Published in:Critical reviews in oncology/hematology 2014-04, Vol.90 (1), p.1-16
Main Authors: Karlic, Heidrun, Herrmann, Harald, Varga, Franz, Thaler, Roman, Reitermaier, Rene, Spitzer, Silvia, Ghanim, Viviane, Blatt, Katharina, Sperr, Wolfgang R, Valent, Peter, Pfeilstöcker, Michael
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - genetics
Autophagy
Demethylating drugs
Epigenesis, Genetic - genetics
Epigenetics
Hematology, Oncology and Palliative Medicine
Humans
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - pathology
Myelodysplastic Syndromes - genetics
Myelodysplastic Syndromes - pathology
Promoter Regions, Genetic - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract 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.
ISSN:1040-8428
1879-0461
DOI:10.1016/j.critrevonc.2013.10.003