title: High prevalence of T cell receptor D delta 2(D delta)J delta rearrangement in CD7-positive early T cell acute lymphoblastic leukemia.
abstract: We have studied the molecular characteristics of the T cell receptor (TcR) genes in 16 patients with CD7+ early T cell acute lymphoblastic leukemia (T-ALL), defined as being positive for CD7 but negative for CD3/4/8, myeloperoxidase (MPO), and CD19/20. Using gene analysis, rearrangement was demonstrated in one patient for immunoglobulin heavy chain (IgH) gene, five for TcR-beta gene, and four for TcR-gamma gene. Fifteen patients (94%) had rearranged band(s) involving the joining region of the TcR-delta chain gene. In nine cases these were the only rearrangements, whereas in six cases TcR-beta and/or TcR-gamma gene rearrangements were found as well. The D delta 2(D delta)J delta 1 rearrangement was demonstrated in 87.5% (14/16) of cases. D delta 2(D delta)J delta 3 was recognized in one patient, D delta 2D delta 3 was found in three, and V(D)DJ using only V delta 2 and V delta 3 was recognized in two patients. We found no V2D delta 3, V3D delta 3, or V1(D)DJ delta rearrangement patterns. Five of nine cases with DDJ delta were positive for cytoplasmic CD3 epsilon(CyCD3 epsilon). Our data suggest that DDJ delta joining occurs at an early stage during T cell differentiation, followed by rearrangements of V delta to the DDJ delta complex. Furthermore, our findings suggest that DDJ delta recombination occurs earlier than expression of CyCD3 epsilon protein products. DDJ delta rearrangements have never been observed in non-T cell malignancies, such as precursor-B-ALL or acute myeloid leukemia. Therefore, detection of DDJ delta rearrangement in the TcR-delta locus is a useful tool to establish lineage and clonality of leukemic cells in the most immature stages of T cell development.
authors.affiliation: First Department of Internal Medicine, Fukuoka University School of Medicine, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Akiyoshi
authors.forename: T
authors.initials: T
authors.lastname: Uchida
authors.forename: J
authors.initials: J
authors.lastname: Okamura
authors.forename: M
authors.initials: M
authors.lastname: Kozuru
authors.forename: J
authors.initials: J
authors.lastname: Nishimura
authors.forename: J H
authors.initials: JH
authors.lastname: Ohyashiki
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Niho
authors.forename: M
authors.initials: M
authors.lastname: Okumura
mesh_terms: D015703:Antigens, CD / Q000032:analysis*; D019011:Antigens, CD7 / Q000032:analysis*; D001483:Base Sequence; D015139:Blotting, Southern; D017931:DNA Primers; D015342:DNA Probes; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D006801:Humans; D016130:Immunophenotyping; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000276:immunology*; D008969:Molecular Sequence Data; D009195:Peroxidase / Q000032:analysis; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D019011:Antigens, CD7; D017931:DNA Primers; D015342:DNA Probes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D009195:Peroxidase