Genome-wide mapping and characterization of notch-regulated long noncoding RNAs in acute leukemia

Thomas Trimarchi, Erhan Bilal, Panagiotis Ntziachristos, Giulia Fabbri, Riccardo Dalla-Favera, Aristotelis Tsirigos*, Iannis Aifantis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

300 Scopus citations

Abstract

Notch signaling is a key developmental pathway that is subject to frequent genetic and epigenetic perturbations in many different human tumors. Here we investigate whether long noncoding RNA (lncRNA) genes, in addition to mRNAs, are key downstream targets of oncogenic Notch1 in human T cell acute lymphoblastic leukemia (T-ALL). By integrating transcriptome profiles with chromatin state maps, we have uncovered many previously unreported T-ALL-specific lncRNA genes, a fraction of which are directly controlled by the Notch1/Rpbjκ activator complex. Finally we have shown that one specific Notch-regulated lncRNA, LUNAR1, is required for efficient T-ALL growth in vitro and in vivo due to its ability to enhance IGF1R mRNA expression and sustain IGF1 signaling. These results confirm that lncRNAs are important downstream targets of the Notch signaling pathway, and additionally they are key regulators of the oncogenic state in T-ALL.

Original languageEnglish (US)
Pages (from-to)593-606
Number of pages14
JournalCell
Volume158
Issue number3
DOIs
StatePublished - Jul 31 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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