title: Vdelta2-Jalpha rearrangements are frequent in precursor-B-acute lymphoblastic leukemia but rare in normal lymphoid cells.
abstract: The frequently occurring T-cell receptor delta (TCRD) deletions in precursor-B-acute lymphoblastic leukemia (precursor-B-ALL) are assumed to be mainly caused by Vdelta2-Jalpha rearrangements. We designed a multiplex polymerase chain reaction tified clonal Vdelta2-Jalpha rearrangements in 141 of 339 (41%) childhood and 8 of 22 (36%) adult precursor-B-ALL. A significant proportion (44%) of Vdelta2-Jalpha rearrangements in childhood precursor-B-ALL were oligoclonal. Sequence analysis showed preferential usage of the Jalpha29 gene segment in 54% of rearrangements. The remaining Vdelta2-Jalpha rearrangements used 26 other Jalpha segments, which included 2 additional clusters, one involving the most upstream Jalpha segments (ie, Jalpha48 to Jalpha61; 23%) and the second cluster located around the Jalpha9 gene segment (7%). Real-time quantitative PCR studies of normal lymphoid cells showed that Vdelta2 rearrangements to upstream Jalpha segments occurred at low levels in the thymus (10(-2) to 10(-3)) and were rare (generally below 10(-3)) in B-cell precursors and mature T cells. Vdelta2-Jalpha29 rearrangements were virtually absent in normal lymphoid cells. The monoclonal Vdelta2-Jalpha rearrangements in precursor-B-ALL may serve as patient-specific targets for detection of minimal residual disease, because they show high sensitivity (10(-4) or less in most cases) and good stability (88% of rearrangements preserved at relapse).
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Szczepanski
authors.forename: Vincent H J
authors.initials: VH
authors.lastname: van der Velden
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Hoogeveen
authors.forename: Maaike
authors.initials: M
authors.lastname: de Bie
authors.forename: Daniëlle C H
authors.initials: DC
authors.lastname: Jacobs
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: van Wering
authors.forename: Jacques J M
authors.initials: JJ
authors.lastname: van Dongen
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015321:Gene Rearrangement; D019676:Genes, T-Cell Receptor delta / Q000235:genetics*; D006801:Humans; D007223:Infant; D008214:Lymphocytes; D025202:Molecular Diagnostic Techniques / Q000379:methods / Q000592:standards; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012680:Sensitivity and Specificity