SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB function and pre-T alpha chain expression

Nat Immunol. 2000 Aug;1(2):138-44. doi: 10.1038/77819.

Abstract

Cooperation between the stem cell leukemia (SCL) transcription factor and its nuclear partners LMO1 or LMO2 induces aggressive T cell acute lymphoblastic leukemia when inappropriately expressed in T cells. This study examined the cellular and molecular targets of the SCL-LMO complex at the preleukemic stage. We show that SCL and its partners are coexpressed in the most primitive thymocytes. Maturation to the pre-T cell stage is associated with a down-regulation of SCL and LMO1 and LMO2, and a concomitant up-regulation of E2A and HEB expression. Moreover, enforced expression of SCL-LMO1 inhibits T cell differentiation and recapitulates a loss of HEB function, causing a deregulation of the transition checkpoint from the CD4-CD8- to CD4+CD8+ stages. Finally, we identify the gene encoding pT alpha as a downstream target of HEB that is specifically repressed by the SCL-LMO complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • CD4 Antigens / genetics
  • Cell Differentiation
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation
  • Helix-Loop-Helix Motifs*
  • Humans
  • LIM Domain Proteins
  • Membrane Glycoproteins / genetics*
  • Metalloproteins / biosynthesis*
  • Metalloproteins / genetics
  • Mice
  • Mice, Transgenic
  • Nuclear Proteins
  • Oncogene Proteins*
  • Proto-Oncogene Proteins*
  • Receptors, Antigen, T-Cell, alpha-beta
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Thymus Gland / cytology
  • Thymus Gland / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Basic Helix-Loop-Helix Transcription Factors
  • CD4 Antigens
  • DNA-Binding Proteins
  • LIM Domain Proteins
  • LMO1 protein, human
  • LMO2 protein, human
  • Lmo1 protein, mouse
  • Lmo2 protein, mouse
  • Membrane Glycoproteins
  • Metalloproteins
  • Nuclear Proteins
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • TCF3 protein, human
  • Tal1 protein, mouse
  • Tcf12 protein, mouse
  • Transcription Factors
  • pre-T cell receptor alpha
  • TAL1 protein, human
  • TCF12 protein, human