title: HBL-3 cell line, derived from precursor B-cell lymphoblastic leukemia, lacks somatic hypermutation of immunoglobulin heavy chain variable region genes.
abstract: Somatic mutation (SM) analysis provides a useful tool for understanding the stages at which neoplastic differentiate from normal B-cells. B-cell precursor neoplasms are considered to be somatically premutational. However, the variable frequency of SM of the variable region (VH) genes has been described in cases of precursor B-cell acute lymphoblastic leukemia (PB-ALL). To better characterize PB-ALL based on the differentiation stage, we investigated the SM of the VH genes expressed by tumor cells of the surface immunoglobulin (sIg)(-) HBL-3 cell line derived from childhood PB-ALL. In the HBL-3 cell line, the rearranged Ig heavy chain VH gene sequence showed no SM in the complementarity-determining regions of 1, 2, and 3, or in the framework regions of 1, 2, and 3 relative to the putative germline VH gene sequences. In addition, the VH segment of HBL-3 cells showed no intraclonal sequence heterogeneity, indicating ongoing SM. Our data demonstrated that HBL-3 cells express unmutated and developmentally regulated rearrangement of VH genes at the stage of B-cell precursor cells. HBL-3 cells, which are derived only from the sIg(-) PB-ALL, showed that SM cannot be recognized in VH genes of tumor cells before the expression of sIg.
authors.affiliation: First Department of Pathology, Fukushima Medical University School of Medicine, 1 Hikariga-oka, Fukushima, 960-1295, Japan. hirohojo@fmu.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hojo
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
authors.forename: Michiko
authors.initials: M
authors.lastname: Sato
authors.forename: Masafumi
authors.initials: M
authors.lastname: Abe
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm