title: Human T cell leukemias with continuous V(D)J recombinase activity for TCR-delta gene deletion.
abstract: The so-called TCR-delta-deleting elements, deltaRec and psiJ alpha, flank the major part of the TCR-delta gene complex. By rearranging to each other, the deltaRec and psiJ alpha gene segments delete the TCR-delta gene complex and prepare the allele for subsequent TCR-alpha rearrangement. This intermediate rearrangement is thought to be a specific rearrangement event. In our studies on TCR-delta deletion mechanisms, we identified several T cell acute lymphoblastic leukemias (T-ALL) with continuous activity of the deltaRec-psiJ alpha rearrangement process. Extensive Southern blot, PCR, and sequencing analyses on the coding joints as well as the signal joints of the deltaRec-psiJ alpha rearrangements in these patients allowed us to prove that this continuous rearrangement activity occurred in the leukemic cells and that these cells, therefore, represent a polyclonal subpopulation within the otherwise monoclonal T-ALL. In additional studies, we also identified a T cell line (DND41) with continuous activity of the deltaRec-psiJ alpha rearrangement process. Our data suggest that the ongoing deltaRec-psiJ alpha gene rearrangements predominantly occur in T cells that cannot express a functional TCR-gammadelta, due to biallelic out-of-frame TCR-delta and/or TCR-gamma gene rearrangements. The described T-ALL and the T cell line can serve as an experimental model in further studies on the regulatory elements involved in the specific deletion of the TCR-delta gene complex.
authors.affiliation: Department of Immunology, Erasmus University Rotterdam and University Hospital Rotterdam, The Netherlands.
authors.forename: T M
authors.initials: TM
authors.lastname: Breit
authors.forename: M C
authors.initials: MC
authors.lastname: Verschuren
authors.forename: I L
authors.initials: IL
authors.lastname: Wolvers-Tettero
authors.forename: E J
authors.initials: EJ
authors.lastname: Van Gastel-Mol
authors.forename: K
authors.initials: K
authors.lastname: Hählen
authors.forename: J J
authors.initials: JJ
authors.lastname: van Dongen
mesh_terms: D004254:DNA Nucleotidyltransferases / Q000235:genetics* / Q000276:immunology; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology; D045567:VDJ Recombinases
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases