TY - JOUR
T1 - Hypermethylation of the VTRNA1-3 Promoter is Associated with Poor Outcome in Lower Risk Myelodysplastic Syndrome Patients
AU - Helbo, Alexandra Søgaard
AU - Treppendahl, Marianne
AU - Aslan, Derya
AU - Dimopoulos, Konstantinos
AU - Nandrup-Bus, Cecilie
AU - Holm, Mette Skov
AU - Andersen, Mette Klarskov
AU - Liang, Gangning
AU - Kristensen, Lasse Sommer
AU - Grønbæk, Kirsten
PY - 2015
Y1 - 2015
N2 - Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders. MDS is frequently associated with deletions on chromosome 5q as well as aberrant DNA methylation patterns including hypermethylation of key tumor suppressors. We have previously shown that hypermethylation and silencing of the non-coding RNA VTRNA2-1 are correlated with poor outcomes in acute myeloid leukemia patients. In this study, we find that VTRNA1-2 and VTRNA1-3, both located on chromosome 5q, can be regulated and silenced by promoter DNA methylation, and that the hypomethylating agent 5-aza-2-deoxycytidine causes reactivation these genes. In normal hematopoiesis, we find that vault RNAs (vtRNAs) show differential methylation between various hematopoietic cell populations, indicating that allele-specific methylation events may occur during hematopoiesis. In addition, we show that VTRNA1-3 promoter hypermethylation is frequent in lower risk MDS patients and is associated with a decreased overall survival.
AB - Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders. MDS is frequently associated with deletions on chromosome 5q as well as aberrant DNA methylation patterns including hypermethylation of key tumor suppressors. We have previously shown that hypermethylation and silencing of the non-coding RNA VTRNA2-1 are correlated with poor outcomes in acute myeloid leukemia patients. In this study, we find that VTRNA1-2 and VTRNA1-3, both located on chromosome 5q, can be regulated and silenced by promoter DNA methylation, and that the hypomethylating agent 5-aza-2-deoxycytidine causes reactivation these genes. In normal hematopoiesis, we find that vault RNAs (vtRNAs) show differential methylation between various hematopoietic cell populations, indicating that allele-specific methylation events may occur during hematopoiesis. In addition, we show that VTRNA1-3 promoter hypermethylation is frequent in lower risk MDS patients and is associated with a decreased overall survival.
U2 - 10.3390/genes6040977
DO - 10.3390/genes6040977
M3 - Journal article
C2 - 26473932
SN - 2073-4425
VL - 6
SP - 977
EP - 990
JO - Genes
JF - Genes
IS - 4
ER -