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Immunoglobulin light chain gene rearrangements display hierarchy in absence of selection for functionality in precursor-B-ALL

Leukemia volume 16, pages 1448–1453 (2002)Cite this article

Abstract

The general order of the immunoglobulin (Ig) gene rearrangement process in human precursor-B cells is largely known. However, the exact Ig rearrangement patterns reflecting this process, especially those of the Ig light chain genes, are not well established. This requires detailed analysis of the gene configuration of all six IGH, IGK and IGL alleles at the single cell level. As such extensive analyses are difficult to perform in a reliable way within a single normal precursor-B cell, we used 169 precursor-B-ALL (ie six pro-B-ALL, 112 common ALL, and 51 pre-B-ALL) as clonal ‘single cell’ model system. The Ig gene recombinations show hierarchy starting with IGHgene rearrangements in all cases, followed by IGK rearrangements, IGKdeletions and/or IGL rearrangements in 71% of cases. IGK deletions were found in the absence of IGL rearrangements in 34% of cases, which might be explained by the continuous recombinase activity in precursor-B-ALL, resulting in ‘end-stage’ IGK rearrangements, together with an apparently limited accessibility of the IGL locus. Remarkably, in 5% of cases IGL rearrangements took place in the absence of IGK rearrangements. In addition we found that in-frame IGH rearrangements are not necessarily required for the induction of Ig light chain gene rearrangements and that IGL rearrangements can be induced irrespective of the frame of the accompanying IGK rearrangements. In conclusion, precursor-B-ALL constitute a model system for studying Ig gene rearrangement processes without selection for functionality of the rearrangements or the influence of somatic hypermutations. Nevertheless, the hierarchy of IGH, IGK and IGL rearrrangements is apparent in precursor-B-ALL.

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Acknowledgements

The authors thank the Dutch Childhood Leukemia Study Group for kindly providing precursor-B-ALL samples. We acknowledge Mrs Ingrid LM Wolvers-Tettero for technical assistance and Mr Tar M van Os and Mrs W Marieke Comans-Bitter for making the figures. This work was supported by the Dutch Cancer Society/Koningin Wilhelmina Fonds (grant SNWLK97–1567).

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Authors and Affiliations

  1. Department of Immunology, Erasmus University Rotterdam/University Hospital Rotterdam, Rotterdam, The Netherlands

    M van der Burg, BH Barendregt, T Szczepañski, AW Langerak & JJM van Dongen

  2. Dept of Pediatric Hematology and Chemotherapy, Silesian Medical Academy, Zabrze, Poland

    T Szczepañski

  3. Dutch Childhood Leukemia Study Group, The Hague, The Netherlands

    ER van Wering

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  1. M van der Burg
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van der Burg, M., Barendregt, B., Szczepañski, T. et al. Immunoglobulin light chain gene rearrangements display hierarchy in absence of selection for functionality in precursor-B-ALL. Leukemia 16, 1448–1453 (2002). https://doi.org/10.1038/sj.leu.2402548

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