Developmental process of the T‐cell receptor α and δ gene assembly in B‐cell precursor acute lymphoblastic leukaemia

Abstract

Summary We analysed the organization of Vδ genes and δ recombining element (δRec) in 27 children with B‐cell precursor acute lymphoblastic leukaemia. Twenty‐two of 54 alleles showed rearrangements of the T‐cell receptor (TCR) δ locus. These rearrangements resulted either from D2Dδ3 (2 alleles) or Vδ2(Dn)Dδ3 (20 alleles) recombinations, and the other Vδ and δRec were not rearranged. Of 23 alleles with deletion of Cδ and rearrangements of Jα. Vδ2, Vδ4 and Vδ5 appeared to rearrange to Jα on five alleles. With regard to the relationship between the rearranged Vα/δ and Jα genes, gene segments 5’to Vδ2 frequently rearranged to Jα more proximal to Cα, whereas Vδ2 and gene segments 3’to Vδ2 showed a tendency to rearrange to Jα distal to Cα. Based on these findings, we suggest that the initial recombination event of the TCR‐α/δ gene may be D2Dδ3 joining, followed by Vδ2 recombination with the D2Dδ3 complex. It was also suggested that use of Vα/δ and Jα/δ may depend on the distance between the involved Vα/δ and Jα/δ at least in B‐lineage cells. These rearrangements in B‐precursor cells appear to be aberrant. However, this recombinational process may be one of the normal differentiation pathways in T‐lineage cells, because cells with a Vδ2(Dn)Dδ3 rearrangement were detected in 0·1–0·01% of normal peripheral mononuclear cells by the polymerase chain reaction. Copyright © 1991, Wiley Blackwell. All rights reserved