Developmental process of the T-cell receptor alpha and delta gene assembly in B-cell precursor acute lymphoblastic leukaemia.
We analysed the organization of V delta genes and delta recombining element (delta Rec) in 27 children with B-cell precursor acute lymphoblastic leukaemia. Twenty-two of 54 alleles showed rearrangements of the T-cell receptor (TCR) delta locus. These rearrangements resulted either from D2D delta 3 (2 alleles) or V delta 2(Dn)D delta 3 (20 alleles) recombinations, and the other V delta and delta Rec were not rearranged. Of 23 alleles with deletion of C delta and rearrangements of J alpha, V delta 2, V delta 4 and V delta 5 appeared to rearrange to J alpha on five alleles. With regard to the relationship between the rearranged V alpha/delta and J alpha genes, gene segments 5' to V delta 2 frequently rearranged to J alpha more proximal to C alpha, whereas V delta 2 and gene segments 3' to V delta 2 showed a tendency to rearrange to J alpha distal to C alpha. Based on these findings, we suggest that the initial recombination event of the TCR-alpha/delta gene may be D2D delta 3 joining, followed by V delta 2 recombination with the D2D delta 3 complex. It was also suggested that use of V alpha/delta and J alpha/delta may depend on the distance between the involved V alpha/delta and J alpha/delta 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 V delta 2(Dn)D delta 3 rearrangement were detected in 0.1-0.01% of normal peripheral mononuclear cells by the polymerase chain reaction.
Hara
J
J
Department of Pediatrics, Osaka University Hospital, Japan.
Kawa-Ha
K
K
Takihara
Y
Y
Yumura-Yagi
K
K
Ishihara
S
S
Tawa
A
A
Mak
T W
TW
Okada
S
S
Gelfand
E W
EW
D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D002648:Child; D004273:DNA, Neoplasm / Q000235:genetics*; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics*; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015183:Restriction Mapping
D004273:DNA, Neoplasm; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta