Berx, Geert

Durinck, Kaat

Martens, Liesbet

Saeys, Yvan

Speleman, Franki

Van Loocke, Wouter

Van Vlierberghe, Pieter

Vandamme, Niels

Vandesompele, Jo

Verboom, Karen

English

Ghent University Academic Bibliography

The TLX1 oncogene modulates the enhancer RNA landscape in T-ALL  Karen Verboom1, Wouter Vanloocke1, Jo Vandesompele1, Niels Vandamme2, Geert Berx2, Yvan Saeys3,4, Liesbet Martens2,4, Pieter Van Vlierberghe1, Frank Speleman1, Kaat Durinck1 1Center for Medical Genetics, Ghent University; Cancer Research Institute Ghent, Ghent, Belgium 2 Molecular and cellular Oncology Lab,  Department of Biomedical Molecular Biology, Ghent Universit; Cancer Research Institute Ghent, Ghent, Belgium  3 Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium 4 Data Mining and Modeling for Biomedicine group, VIB Center for Inflammation Research, Ghent, Belgium   T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of blood cancer resulting from malignant transformation of a T-cell precursor. Several driver oncogenes, including the TLX1 transcription factor, have been identified as early events that cooperate with other genetic aberrations in the leukemic transformation of progenitor T-cells. Long non-coding RNAs (lncRNAs) have recently emerged as key players in cancer. In a first step towards unraveling the role of lncRNAs in T-ALL, we established T-ALL subgroup-specific lncRNA expression patterns (Wallaert et al., 2017). We also established the TLX1 regulome through integration of TLX1 and H3K27ac ChIP-sequencing with transcriptome data of ALL-SIL leukemic cells upon TLX1 knockdown (Durinck et al., Leukemia, 2015) and showed a crucial role for TLX1 in regulation of super-enhancer sites and a key set of T-ALL tumor suppressor genes. Next, we performed further in-depth analysis of the TLX1 regulome through an integrative (epi)genomics approach combining polyA+ and total RNA sequencing of ALL-SIL with TLX1 knockdown and primary T-ALL patients (n=64, including 17 TLX-subtype patients) as well as ATAC- and ChIP-sequencing (TLX1, H3K27ac, H3K4me1, H3K4me3). We observed a strong association of TLX1 to enhancer lncRNAs (eRNAs) sites. Moreover, we also identified a set of previously unannotated lncRNAs regulated by TLX1. Finally, using the ChromiumTM single cell device we performed single cell transcriptome analysis on ALL-SIL cells to better understand TLX1 knock-down effects on target genes. In conclusion, our works reveals for the first time a comprehensive view on the enhancer landscape and lncRNAome regulated by TLX1 in T-ALL and provides novel therapeutic avenues for targeted treatment of TLX positive T-ALL.    

The TLX1 oncogene modules the enhancer RNA landscape in T-ALL

https://biblio.ugent.be/publication/8558289/file/8558291

The TLX1 oncogene modules the enhancer RNA landscape in T-ALL

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Ghent University Academic Bibliography