PUBLICATION

Aberrant activation of the GIMAP enhancer by oncogenic transcription factors in T-cell acute lymphoblastic leukemia

Authors
Liau, W.S., Tan, S.H., Ngoc, P.C., Wang, C.Q., Tergaonkar, V., Feng, H., Gong, Z., Osato, M., Look, A.T., Sanda, T.
ID
ZDB-PUB-161229-2
Date
2017
Source
Leukemia   31(8): 1798-1807 (Journal)
Registered Authors
Gong, Zhiyuan, Liau, Wei-Siang, Look, A. Thomas, Sanda, Takaomi
Keywords
none
MeSH Terms
  • Humans
  • Mice
  • Enhancer Elements, Genetic/physiology*
  • Membrane Proteins/genetics*
  • Cell Line, Tumor
  • Proto-Oncogene Proteins/physiology*
  • Transcription Factors/physiology*
  • GTP-Binding Proteins/genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/etiology*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics
  • Mice, Inbred C57BL
  • Zebrafish
  • Basic Helix-Loop-Helix Transcription Factors/physiology*
  • Animals
  • Multigene Family
(all 15)
PubMed
28028313 Full text @ Leukemia
Abstract
The transcription factor TAL1/SCL is one of the most prevalent oncogenes in T-cell acute lymphoblastic leukemia (T-ALL), a malignant disorder resulting from leukemic transformation of thymus T-cell precursors. TAL1 is normally expressed in hematopoietic stem cells (HSCs) but is silenced in immature thymocytes. We hypothesize that TAL1 contributes to leukemogenesis by activating genes that are normally repressed in immature thymocytes. Herein, we identified a novel TAL1-regulated super-enhancer controlling the GIMAP locus, which resides within an insulated chromosomal locus in T-ALL cells. The GIMAP genes are expressed in HSCs and mature T-cells but are downregulated during the immature stage of thymocyte differentiation. The GIMAP enhancer is activated by TAL1, RUNX1 and GATA3 in human T-ALL cells but is repressed by E-proteins. Overexpression of human GIMAP genes in immature thymocytes alone does not induce tumorigenesis but accelerates leukemia development in zebrafish. Our results demonstrate that aberrant activation of the GIMAP enhancer contributes to T-cell leukemogenesis.Leukemia accepted article preview online, 28 December 2016. doi:10.1038/leu.2016.392.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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Citation
Liau, W.S., Tan, S.H., Ngoc, P.C., Wang, C.Q., Tergaonkar, V., Feng, H., Gong, Z., Osato, M., Look, A.T., Sanda, T. (2017) Aberrant activation of the GIMAP enhancer by oncogenic transcription factors in T-cell acute lymphoblastic leukemia. Leukemia. 31(8):1798-1807.