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

Karen Verboom UGent (2018)
abstract
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.
Please use this url to cite or link to this publication:
author
organization
year
type
conference (poster)
publication status
published
subject
keyword
T-ALL, lncRNAs, super-enhancer, sequencing
conference name
Keystone: chromatin architecture and chromosome organization
conference organizer
Edith Heard and Peter Fraser
conference location
Whistler, Canada
conference start
2018-03-23
conference end
2018-03-27
UGent publication?
yes
classification
U
id
8558289
handle
http://hdl.handle.net/1854/LU-8558289
date created
2018-04-04 06:51:14
date last changed
2018-04-04 06:55:07
@inproceedings{8558289,
  abstract     = {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.},
  author       = {Verboom, Karen},
  keyword      = {T-ALL,lncRNAs,super-enhancer,sequencing},
  location     = {Whistler, Canada},
  title        = {The TLX1 oncogene modules the enhancer RNA landscape in T-ALL},
  year         = {2018},
}

Chicago
Verboom, Karen. 2018. β€œThe TLX1 Oncogene Modules the Enhancer RNA Landscape in T-ALL.” In .
APA
Verboom, K. (2018). The TLX1 oncogene modules the enhancer RNA landscape in T-ALL. Presented at the Keystone: chromatin architecture and chromosome organization.
Vancouver
1.
Verboom K. The TLX1 oncogene modules the enhancer RNA landscape in T-ALL. 2018.
MLA
Verboom, Karen. β€œThe TLX1 Oncogene Modules the Enhancer RNA Landscape in T-ALL.” 2018. Print.