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

Crit Rev Oncol Hematol 2014 Apr 12;90(1):1-16. Epub 2013 Oct 12.

Ludwig Boltzmann Cluster Oncology, Vienna, Austria; Ludwig Boltzmann Institute for Leukemia Research and Hematology, Hanusch Hospital, Vienna, Austria; 3rd Medical Department, Hanusch Hospital, Vienna, Austria.

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.

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S10408428130021
Publisher Site
http://dx.doi.org/10.1016/j.critrevonc.2013.10.003DOI Listing
April 2014

Publication Analysis

Top Keywords

fas dapk1
8
myeloid leukemia
8
neoplastic cells
8
mds aml
8
myelodysplastic syndromes
8
acute myeloid
8
mds
5
patients low-risk
4
cell lines
4
cells patients
4
apoptosis-mediators fas
4
low-risk mds
4
epigenetically silenced
4
dapk1 represents
4
mds epigenetically
4
represents critical
4
mechanism drug-induced
4
gene demethylation
4
apoptosis leukemic
4
association autophagy
4

Similar Publications