Hypermethylation of the VTRNA1-3 Promoter is Associated with Poor Outcome in Lower Risk Myelodysplastic Syndrome Patients

Alexandra Søgaard Helbo, Marianne Treppendahl, Derya Aslan, Konstantinos Dimopoulos, Cecilie Nandrup-Bus, Mette Skov Holm, Mette Klarskov Andersen, Gangning Liang, Lasse Sommer Kristensen, Kirsten Grønbæk

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalGenes
Volume6
Issue number4
Pages (from-to)977-90
Number of pages14
ISSN2073-4425
DOIs
Publication statusPublished - 2015

Fingerprint

Dive into the research topics of 'Hypermethylation of the VTRNA1-3 Promoter is Associated with Poor Outcome in Lower Risk Myelodysplastic Syndrome Patients'. Together they form a unique fingerprint.

Cite this