title: A common V delta 2-D delta 2-D delta 3 T cell receptor gene rearrangement in precursor B acute lymphoblastic leukaemia.
abstract: Despite their apparent commitment to the B lymphocytic lineage, human precursor B cell acute lymphoblastic leukaemias (ALL) frequently rearrange their T cell antigen receptor (TCR) alpha, beta and gamma chain genes. Since these three genes are active sites of rearrangement in precursor B cell neoplasms, it seemed that the recently discovered fourth TCR gene, delta, might be similarly rearranged. To investigate this possibility, a series of precursor B cell leukaemias was analysed for rearrangements at the delta chain gene locus, using probes of the variable, joining, and constant regions of the delta chain gene. The majority of precursor B cell ALLs in this series (25/32, 78%) showed rearrangement or deletion of one or more TCR delta genes. This contrasts sharply with a series of 16 mature B cell neoplasms (chronic lymphocytic leukaemia) in which no TCR delta gene rearrangements were detected. An unusual TCR delta rearrangement, rarely observed in normal or neoplastic T cells, was seen in the majority (14/18) of precursor B cell ALLs with TCR delta rearrangements. In contrast to the utilization ov V delta 1 in T cell ALL, detailed restriction mapping of precursor B ALL revealed an incomplete rearrangement without involvement of J delta segments. Direct genomic sequencing was performed on one example and demonstrated a nonproductive V delta 2-D delta 2-D delta 3 recombination in this precursor B ALL. We conclude that the TCR delta chain gene is an active locus in precursor B cell neoplasia, involves an unusual type of rearrangement and provides a clonal tumour marker for diagnosis of precursor B ALL.
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Md.
authors.forename: T
authors.initials: T
authors.lastname: Yano
authors.forename: A
authors.initials: A
authors.lastname: Pullman
authors.forename: R
authors.initials: R
authors.lastname: Andrade
authors.forename: M
authors.initials: M
authors.lastname: Uppenkamp
authors.forename: J P
authors.initials: JP
authors.lastname: de Villartay
authors.forename: G
authors.initials: G
authors.lastname: Reaman
authors.forename: S
authors.initials: S
authors.lastname: Crush-Stanton
authors.forename: D I
authors.initials: DI
authors.lastname: Cohen
authors.forename: M
authors.initials: M
authors.lastname: Raffeld
authors.forename: J
authors.initials: J
authors.lastname: Cossman
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D002051:Burkitt Lymphoma / Q000235:genetics*; D015321:Gene Rearrangement / Q000502:physiology; D015329:Gene Rearrangement, T-Lymphocyte / Q000502:physiology*; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000502:physiology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000502:physiology; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction