Unique long non-coding RNA expression signature in ETV6/RUNX1-driven B-cell precursor acute lymphoblastic leukemia

• Published in: Oncotarget Vol. 7; no. 45; pp. 73769 - 73780
• Main Authors: Ghazavi, Farzaneh, De Moerloose, Barbara, Van Loocke, Wouter, Wallaert, Annelynn, Helsmoortel, Hetty H, Ferster, Alina, Bakkus, Marleen, Plat, Geneviève, Delabesse, Eric, Uyttebroeck, Anne, Van Nieuwerburgh, Filip, Deforce, Dieter, Van Roy, Nadine, Speleman, Frank, Benoit, Yves, Lammens, Tim, Van Vlierberghe, Pieter
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 08.11.2016
• Subjects: Cell Line, Tumor; Child; Computational Biology - methods; Core Binding Factor Alpha 2 Subunit - genetics; Gene Expression; Gene Expression Regulation, Leukemic; Humans; Molecular Sequence Annotation; Oncogene Proteins, Fusion - genetics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Research Paper; RNA Interference; RNA, Long Noncoding - genetics; Sequence Analysis, RNA; Transcriptome; ETV6/RUNX1; lncRNA; BCP-ALL
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.12063

Overwhelming evidence indicates that long non-coding RNAs have essential roles in tumorigenesis. Nevertheless, their role in the molecular pathogenesis of pediatric B-cell precursor acute lymphoblastic leukemia has not been extensively explored. Here, we conducted a comprehensive analysis of the long non-coding RNA transcriptome in ETV6/RUNX1-positive BCP-ALL, one of the most frequent subtypes of pediatric leukemia. First, we used primary leukemia patient samples to identify an ETV6/RUNX1 specific expression signature consisting of 596 lncRNA transcripts. Next, integration of this lncRNA signature with RNA sequencing of BCP-ALL cell lines and lncRNA profiling of an in vitro model system of ETV6/RUNX1 knockdown, revealed that lnc-NKX2-3-1, lnc-TIMM21-5, lnc-ASTN1-1 and lnc-RTN4R-1 are truly regulated by the oncogenic fusion protein. Moreover, sustained inactivation of lnc-RTN4R-1 and lnc-NKX2-3-1 in ETV6/RUNX1 positive cells caused profound changes in gene expression. All together, our study defined a unique lncRNA expression signature associated with ETV6/RUNX1-positive BCP-ALL and identified lnc-RTN4R-1 and lnc-NKX2-3-1 as lncRNAs that might be functionally implicated in the biology of this prevalent subtype of human leukemia.