Identification of novel lncRNAs regulated by the TAL1 complex in T-cell acute lymphoblastic leukemia

Leukemia. 2018 Oct;32(10):2138-2151. doi: 10.1038/s41375-018-0110-4. Epub 2018 Mar 26.

Abstract

TAL1/SCL is one of the most prevalent oncogenes in T-cell acute lymphoblastic leukemia (T-ALL). TAL1 and its regulatory partners (GATA3, RUNX1, and MYB) positively regulate each other and coordinately regulate the expression of their downstream target genes in T-ALL cells. However, long non-coding RNAs (lncRNAs) regulated by these factors are largely unknown. Here we established a bioinformatics pipeline and analyzed RNA-seq datasets with deep coverage to identify lncRNAs regulated by TAL1 in T-ALL cells. Our analysis predicted 57 putative lncRNAs that are activated by TAL1. Many of these transcripts were regulated by GATA3, RUNX1, and MYB in a coordinated manner. We identified two novel transcripts that were activated in multiple T-ALL cell samples but were downregulated in normal thymocytes. One transcript near the ARID5B gene locus was specifically expressed in TAL1-positive T-ALL cases. The other transcript located between the FAM49A and MYCN gene locus was also expressed in normal hematopoietic stem cells and T-cell progenitor cells. In addition, we identified a subset of lncRNAs that were negatively regulated by TAL1 and positively regulated by E-proteins in T-ALL cells. This included a known lncRNA (lnc-OAZ3-2:7) located near the RORC gene, which was expressed in normal thymocytes but repressed in TAL1-positive T-ALL cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Core Binding Factor Alpha 2 Subunit / genetics
  • DNA-Binding Proteins / genetics
  • GATA3 Transcription Factor / genetics
  • Gene Expression Regulation, Leukemic / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Mice
  • N-Myc Proto-Oncogene Protein / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • RNA, Long Noncoding / genetics*
  • T-Cell Acute Lymphocytic Leukemia Protein 1 / genetics*
  • Thymocytes / physiology

Substances

  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Intracellular Signaling Peptides and Proteins
  • N-Myc Proto-Oncogene Protein
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RNA, Long Noncoding
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • TAL1 protein, human