title: Third complementarity determining region (CDR III) sequence analysis in childhood B-lineage acute lymphoblastic leukaemia: implications for the design of oligonucleotide probes for use in monitoring minimal residual disease.
abstract: The genetic sequence of the third complementarity determining region (CDR III) of the immunoglobulin heavy chain (IgH) gene was analysed in 55 rearranged alleles from 36 children presenting with B-lineage acute lymphoblastic leukaemia (ALL). This confirmed the unique nature of these rearrangements. However, contrary to the hypothesis that the CDR III is produced by a random process of rearrangement, biased utilisation of diversity (D) segments and of joining (J) regions 4, 5 and 6 was demonstrated. Moreover, preferred sequence boundaries were seen in J regions 1 to 5 and were suggested at the 3'-end of certain D regions, notably D21/9 and DK1. Similar patterns of rearrangement have been noted in normal B-lymphocyte clones. Together with relatively limited N nucleotide addition, these factors may restrict the potential sequence variability at the D-N-J junction. The occurrence of clonal progression by secondary gene rearrangements, such as V-V replacement, favours the use of this site when designing clone-specific oligonucleotide probes for use in monitoring minimal residual disease (MRD). In cases where biased features of D-J rearrangement are shared by both the leukaemic and normal B-lymphocyte clones this could reduce the sensitivity of these probes in detecting low levels of residual disease.
authors.affiliation: Department of Pathology, Bristol University Medical School, University Walk, UK.
authors.forename: C G
authors.initials: CG
authors.lastname: Steward
authors.forename: M N
authors.initials: MN
authors.lastname: Potter
authors.forename: A
authors.initials: A
authors.lastname: Oakhill
mesh_terms: D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains; D009838:Oligodeoxyribonucleotides