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

par Ghazavi, Farzaneh;Uyttebroeck, Anne;Van Nieuwerburgh, Filip;Deforce, Dieter;Van Roy, Nadine;Speleman, Frank;Benoît, Yves;Lammens, Tim;Van Vlierberghe, Pieter;De Moerloose, Barbara M J B.;Van Loocke, Wouter;Wallaert, Annelynn;Helsmoortel, Hetty;Ferster, Alina ;Bakkus, Marleen;Plat, Geneviève;Delabesse, Eric
Référence Oncotarget, 7, 45, page (73769-73780)
Publication Publié, 2016-11

Article révisé par les pairs

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Résumé :

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.