ArticleMolecular medicine (Cambridge, Mass.)
Analysis of expressed and non-expressed IGK locus rearrangements in chronic lymphocytic leukemia.
Article in Molecular medicine (Cambridge, Mass.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 16 citations in OpenAlex.
- ABO: A 3D stroma-supported culture platform enabling full human B-lymphopoiesis for disease modeling and gene therapy development.Cell reports. Medicine · 2026Article
- Longitudinal Dynamics of Human B-Cell Response at the Single-Cell Level in Response to Tdap Vaccination.Vaccines · 2021Article
- Additional trisomies amongst patients with chronic lymphocytic leukemia carrying trisomy 12: the accompanying chromosome makes a difference.Haematologica · 2016Article
- B cell receptor light chain repertoires show signs of selection with differences between groups of healthy individuals and SLE patients.Molecular immunology · 2012Article
- Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: ontogenetic implications.Leukemia · 2012Article
- Partial versus productive immunoglobulin heavy locus rearrangements in chronic lymphocytic leukemia: implications for B-cell receptor stereotypy.Molecular medicine (Cambridge, Mass.) · 2012Article
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11 authors at 3 institutions in 1 country.
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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.
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