Title: The Notch driven long non-coding RNA repertoire in T-cell acute lymphoblastic leukemia
Authors: Durinck, Kaat
Wallaert, Annelynn
Van de Walle, Inge
Van Loocke, Wouter
Volders, Pieter-Jan
Vanhauwaert, Suzanne
Geerdens, Ellen
Benoit, Yves
Van Roy, Nadine
Poppe, Bruce
Soulier, Jean
Cools, Jan
Mestdagh, Pieter
Vandesompele, Jo
Rondou, Pieter
Van Vlierberghe, Pieter
Taghon, Tom
Speleman, Frank # ×
Issue Date: Dec-2014
Publisher: Il Pensiero Scientifico
Series Title: Haematologica vol:99 issue:12 pages:1808-16
Article number: 10.3324/haematol.2014.115683
Abstract: Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting a role as an essential driver for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34(+) thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from ex vivo isolated Notch active CD34(+) and Notch inactive CD4(+)CD8(+) thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publicly available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T cells. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way for the development of novel therapeutic strategies that target hyperactive Notch signaling in human T-cell acute lymphoblastic leukemia.
ISSN: 0390-6078
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory of Molecular Biology of Leukemia
× corresponding author
# (joint) last author

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