Human T cell leukemias with continuous V(D)J recombinase activity for TCR-delta gene deletion

J Immunol. 1997 Nov 1;159(9):4341-9.

Abstract

The so-called TCR-delta-deleting elements, deltaRec and psiJ alpha, flank the major part of the TCR-delta gene complex. By rearranging to each other, the deltaRec and psiJ alpha gene segments delete the TCR-delta gene complex and prepare the allele for subsequent TCR-alpha rearrangement. This intermediate rearrangement is thought to be a specific rearrangement event. In our studies on TCR-delta deletion mechanisms, we identified several T cell acute lymphoblastic leukemias (T-ALL) with continuous activity of the deltaRec-psiJ alpha rearrangement process. Extensive Southern blot, PCR, and sequencing analyses on the coding joints as well as the signal joints of the deltaRec-psiJ alpha rearrangements in these patients allowed us to prove that this continuous rearrangement activity occurred in the leukemic cells and that these cells, therefore, represent a polyclonal subpopulation within the otherwise monoclonal T-ALL. In additional studies, we also identified a T cell line (DND41) with continuous activity of the deltaRec-psiJ alpha rearrangement process. Our data suggest that the ongoing deltaRec-psiJ alpha gene rearrangements predominantly occur in T cells that cannot express a functional TCR-gammadelta, due to biallelic out-of-frame TCR-delta and/or TCR-gamma gene rearrangements. The described T-ALL and the T cell line can serve as an experimental model in further studies on the regulatory elements involved in the specific deletion of the TCR-delta gene complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Nucleotidyltransferases / genetics*
  • DNA Nucleotidyltransferases / immunology
  • Gene Deletion*
  • Gene Expression Regulation, Neoplastic
  • Gene Rearrangement, T-Lymphocyte*
  • Genes, Immunoglobulin
  • Humans
  • Leukemia, T-Cell / genetics*
  • Leukemia, T-Cell / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • VDJ Recombinases

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • DNA Nucleotidyltransferases
  • VDJ Recombinases