title: Analysis of expressed and non-expressed IGK locus rearrangements in chronic lymphocytic leukemia.
abstract: Immunoglobulin kappa (IGK) locus rearrangements were analyzed in parallel on cDNA/genomic DNA in 188 kappa- and 103 lambda-chronic lymphocytic leukemia (CLL) cases. IGKV-KDE and IGKJ-C-intron-KDE rearrangements were also analyzed on genomic DNA. In kappa-CLL, only 3 of 188 cases carried double in-frame IGKV-J transcripts: in such cases, the possibility that leukemic cells expressed more than one kappa chain cannot be excluded. Twenty-eight kappa-CLL cases also carried nonexpressed (nontranscribed and/or out-of-frame) IGKV-J rearrangements. Taking IGKV-J, IGKV-KDE, and IGKJ-C-intron-KDE rearrangements together, 38% of kappa-CLL cases carried biallelic IGK locus rearrangements. In lambda-CLL, 69 IGKV-J rearrangements were detected in 64 of 103 cases (62%); 24 rearrangements (38.2%) were in-frame. Four cases carried in-frame IGKV-J transcripts but retained monotypic light-chain expression, suggesting posttranscriptional regulation of allelic exclusion. In all, taking IGKV-J, IGKV-KDE, and IGKJ-C-intron-KDE rearrangements together, 97% of lambda-CLL cases had at least 1 rearranged IGK allele, in keeping with normal cells. IG repertoire comparisons in kappa- versus lambda-CLL revealed that CLL precursor cells tried many rearrangements on the same IGK allele before they became lambda producers. Thirteen of 28 and 26 of 69 non-expressed sequences in, respectively, kappa- or lambda-CLL had < 100% homology to germline. This finding might be considered as evidence for secondary rearrangements occurring after the onset of somatic hypermutation, at least in some cases. The inactivation of potentially functional IGKV-J joints by secondary rearrangements indicates active receptor editing in CLL and provides further evidence for the role of antigen in CLL immunopathogenesis.
authors.affiliation: Hematology Department, Nikea General Hospital, Piraeus, Greece. cbelessi@otenet.gr
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Belessi
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.forename: Anastasia
authors.initials: A
authors.lastname: Hadzidimitriou
authors.forename: Katerina
authors.initials: K
authors.lastname: Hatzi
authors.forename: Tatjana
authors.initials: T
authors.lastname: Smilevska
authors.forename: Niki
authors.initials: N
authors.lastname: Stavroyianni
authors.forename: Fotini
authors.initials: F
authors.lastname: Marantidou
authors.forename: George
authors.initials: G
authors.lastname: Paterakis
authors.forename: Athanasios
authors.initials: A
authors.lastname: Fassas
authors.forename: Achilles
authors.initials: A
authors.lastname: Anagnostopoulos
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Laoutaris
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002478:Cells, Cultured; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology*; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017393:RNA Editing / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D011995:Recombination, Genetic / Q000276:immunology
chemical_list: D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D011947:Receptors, Antigen, B-Cell