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Crosslineage TCR delta rearrangements occur shortly after the DJ joinings of the IgH genes in childhood precursor B ALL and display age‐specific characteristics
Author(s) -
Schneider Monika,
Panzer Simon,
Stolz Frank,
Fischer Susanna,
Gadner Helmut,
PanzerGrümayer E. Renate
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.3653179.x
Subject(s) - biology , gene rearrangement , t cell receptor , gene , terminal deoxynucleotidyl transferase , recombination signal sequences , microbiology and biotechnology , genetics , t cell , apoptosis , immune system , tunel assay
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 Vδ2–Dδ3 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 Vδ2–Dδ3 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 Vδ2–Dδ3 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.