Crosslineage TCR delta rearrangements occur shortly after the DJ joinings of the IgH genes in childhood precursor B ALL and display age-specific characteristics

Br J Haematol. 1997 Oct;99(1):115-21. doi: 10.1046/j.1365-2141.1997.3653179.x.

Abstract

In order to test the hypothesis that the most immature T-cell receptor (TCR) rearrangements occur after the DJ joining of the immunoglobulin heavy chain genes (IgH), we analysed the TCR Vdelta2-Ddelta3 rearrangements in precursor B-cell leukaemias (PBC ALL) from 25 children younger than 3 years at disease onset and found that most of the junctional regions had N nucleotides inserted. We then selected 14 of these PCB ALLs for DJH (DJ joining of the IgH) characterization. These joining regions showed homology-directed recombination and lack of N regions, indicating absence of terminal deoxynucleotidyl transferase (TdT) activity during their rearrangement. Most leukaemias with a DJH rearrangement without N region have no, or only one, nucleotide in the joining regions of their Vdelta2-Ddelta3 rearrangements. The N regions of the TCR delta rearrangements displayed 'age-specific' differences: in children younger than 3 years of age the N regions were shorter than in those older than 3 years, and the rearrangements frequently contained complete segments. We conclude that the Vdelta2-Ddelta3 rearrangement in childhood PCB ALLs is an early event following DJH rearrangement and that it occurs shortly before or after the first hit, leading to malignant transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Base Sequence
  • Child
  • Child, Preschool
  • Gene Rearrangement, delta-Chain T-Cell Antigen Receptor
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Infant
  • Molecular Sequence Data
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*

Substances

  • Immunoglobulin Heavy Chains