title: Characterization of the immunoglobulin heavy chain complementarity determining region (CDR)-III sequences from human B cell precursor acute lymphoblastic leukemia cells.
abstract: Sequence analysis of the immunoglobulin heavy chain complementarity determining region (CDR)-III of B-lineage cells at various stages has provided important insights concerning B cell maturation and selection. Knowledge of human CDR-III sequences has been relatively limited compared with that of the murine system. We analyzed the CDR-III sequences of B cell precursor acute lymphoblastic leukemia (pre-B ALL) cells in 23 newly diagnosed and 10 relapsed patients, in order to elucidate the organization of CDR-III in B cell precursors. We found a very low frequency of somatic mutations in D and JH regions, preferential use of DLR, DXP, DHQ52, and DN elements, and of 3' side JH segments, and no predominant usage of D coding frames. Unusual joinings such as VH-D-D-JH and VH-JH were observed in three, and one sequences, respectively. We compared the CDR-III sequences derived from 10 patients between diagnosis and relapse. Two of them had three spots of mutated nucleotides at relapse, all of which were found in the N region near the D segments. Our data showed the possibility of somatic mutation at relapse, in addition to developmentally regulated rearrangement of the immunoglobulin gene at the stage of B cell precursors.
authors.affiliation: Department of Medicine, Branch Hospital Nagoya University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kiyoi
authors.forename: T
authors.initials: T
authors.lastname: Naoe
authors.forename: K
authors.initials: K
authors.lastname: Horibe
authors.forename: R
authors.initials: R
authors.lastname: Ohno
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000276:immunology*; D012008:Recurrence
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region