The enhancer RNA ARIEL activates the oncogenic transcriptional program in T-cell acute lymphoblastic leukemia

Blood. 2019 Jul 18;134(3):239-251. doi: 10.1182/blood.2018874503. Epub 2019 May 10.


The oncogenic transcription factor TAL1 regulates the transcriptional program in T-ALL. ARID5B is one of the critical downstream targets of TAL1, which further activates the oncogenic regulatory circuit in T-ALL cells. Here, we elucidated the molecular functions of the noncoding RNA, ARID5B-inducing enhancer associated long noncoding RNA (ARIEL), in T-ALL pathogenesis. We demonstrated that ARIEL is specifically activated in TAL1 + T-ALL cases, and its expression is associated with ARID5B enhancer activity. ARIEL recruits mediator proteins to the ARID5B enhancer, promotes enhancer-promoter interactions, and activates the expression of ARID5B, thereby positively regulating the TAL1-induced transcriptional program and the MYC oncogene. The TAL1 complex coordinately regulates the expression of ARIEL Knockdown of ARIEL inhibits cell growth and survival of T-ALL cells in culture and blocks disease progression in a murine xenograft model. Our results indicate that ARIEL plays an oncogenic role as an enhancer RNA in T-ALL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / genetics
  • Chromatin Immunoprecipitation Sequencing
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Leukemic*
  • Gene Knockdown Techniques
  • Gene Targeting
  • Heterografts
  • Humans
  • Mice
  • Models, Biological
  • Multiprotein Complexes
  • Oncogenes
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Long Noncoding / genetics*
  • T-Cell Acute Lymphocytic Leukemia Protein 1 / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic*


  • ARID5B protein, human
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • RNA, Long Noncoding
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcription Factors