Crosslineage TCR delta rearrangements occur shortly after the DJ joinings of the IgH genes in childhood precursor B ALL and display age-specific characteristics.
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.
Schneider
M
M
Children's Cancer Research Institute, St Anna Children's Hospital, University of Vienna, Austria.
Panzer
S
S
Stolz
F
F
Fischer
S
S
Gadner
H
H
Panzer-Grümayer
E R
ER
D000293:Adolescent; D000367:Age Factors; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007223:Infant; D008969:Molecular Sequence Data; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*
D007143:Immunoglobulin Heavy Chains