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Precursor-B-ALL with DH–JH gene rearrangements have an immature immunogenotype with a high frequency of oligoclonality and hyperdiploidy of chromosome 14

Leukemia volume 15, pages 1415–1423 (2001)Cite this article

Abstract

The IGH gene configuration was investigated in 97 childhood precursor-B-ALL patients at initial diagnosis. Rearrangements were found by Southern blotting in all but three patients (97%) and in 30 cases (31%) we observed oligoclonal IGH gene rearrangements. Heteroduplex PCR analysis revealed at least one clonal PCR product in all Southern blot-positive cases. In 89 patients (92%) complete V(D)J rearrangements were found, while incomplete DH–JH rearrangements occurred in only 21 patients (22%). In 5% of cases the DH–JH rearrangements were the sole IGH gene rearrangements. Sequence analysis of the 31 identified incomplete rearrangements revealed preferential usage of segments from the DH2, DH3 and DH7 families (78%). While DH2 and DH3 gene rearrangements occur frequently in normal B cells and B cell precursors, the relatively frequent usage of DH7–27 (19%) in precursor-B-ALL patients is suggestive of leukemic transformation during prenatal lymphopoiesis. Among JH gene segments in the incomplete DH–JH rearrangements, the JH6 segment was significantly overrepresented (61%). This observation together with the predominant usage of the most upstream DH genes indicates that many of the identified clonal DH–JH gene rearrangements in precursor-B-ALL probably represent secondary recombinations, having deleted pre-existing DH–JH joinings. The patients with incomplete DH–JH gene rearrangements were frequently characterized by hyperdiploid karyotype with additional copies of chromosome 14 and/or by IGH oligoclonality. The presence of incomplete DH–JH joinings was also significantly associated with a less mature immunogenotype: overrepresentation of VH6–1 gene segment usage, absence of biallelic TCRD deletions, and low frequency of TCRG gene rearrangements. This immature immunogenotype of precursor-B-ALL with incomplete IGH gene rearrangements was not associated with more aggressive disease.

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Acknowledgements

We are grateful to Prof dr R Benner and Prof dr D Sońta-Jakimczyk for their continuous support, Dr AW Langerak for critical reading of the manuscript, Mr TM van Os and Mrs WM Comans-Bitter for preparation of the figures and Mrs JA Boon for her secretarial support. R Slater and E van den Berg for the Dutch Workgroup on Cancer Genetics and Cytogenetics are acknowledged for sharing the cytogenetic data. We thank the Dutch Childhood Leukemia Study Group for kindly providing precursor-B-ALL cell samples. Board members of the DCLSG are PJ van Dijken, K Hählen, WA Kamps, ETh Korthof, FAE Nabben, A Postma, JA Rammeloo, GAM de Vaan, AJP Veerman and RS Weening.

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Authors and Affiliations

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

    T Szczepański, MJ Willemse & JJM van Dongen

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

    T Szczepański

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

    ER van Wering, JF van Weerden & WA Kamps

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Szczepański, T., Willemse, M., van Wering, E. et al. Precursor-B-ALL with DH–JH gene rearrangements have an immature immunogenotype with a high frequency of oligoclonality and hyperdiploidy of chromosome 14. Leukemia 15, 1415–1423 (2001). https://doi.org/10.1038/sj.leu.2402206

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