title: Hypermethylation of the VTRNA1-3 Promoter is Associated with Poor Outcome in Lower Risk Myelodysplastic Syndrome Patients.
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.
authors.affiliation: Department of Hematology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. alexandra.soegaard@regionh.dk.
authors.forename: Alexandra Søgaard
authors.initials: AS
authors.lastname: Helbo
authors.affiliation: Department of Hematology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. marianne.treppendahl@gmail.com.
authors.forename: Marianne
authors.initials: M
authors.lastname: Treppendahl
authors.affiliation: Department of Hematology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. qcl997@alumni.ku.dk.
authors.forename: Derya
authors.initials: D
authors.lastname: Aslan
authors.affiliation: Department of Hematology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. konstantinos.dimopoulos@regionh.dk.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Dimopoulos
authors.affiliation: Department of Hematology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. cecilie.nandrup-bus@regionh.dk.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Nandrup-Bus
authors.affiliation: Department of Hematology, Aarhus University Hospital, Tage Hansens Gade 2, 8000 Aarhus C, Denmark. mettehlm@rm.dk.
authors.forename: Mette Skov
authors.initials: MS
authors.lastname: Holm
authors.affiliation: Department of Clinical Genetics, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. mette.klarskov.andersen@regionh.dk.
authors.forename: Mette Klarskov
authors.initials: MK
authors.lastname: Andersen
authors.affiliation: Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA. gliang@usc.edu.
authors.forename: Gangning
authors.initials: G
authors.lastname: Liang
authors.affiliation: Department of Hematology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. lasse.sommer.kristensen@regionh.dk.
authors.forename: Lasse Sommer
authors.initials: LS
authors.lastname: Kristensen
authors.affiliation: Department of Hematology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. kirsten.groenbaek@regionh.dk.|Danstem, University of Copenhagen, Blegdamsvej, 2200 Copenhagen N, Denmark. kirsten.groenbaek@regionh.dk.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Grønbæk
keywords: Azanucleosides; DNA methylation; Myelodysplastic syndrome; non-coding RNA; vault RNA