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Acute Leukemias

Chromosome 14 copy number-dependent IGH gene rearrangement patterns in high hyperdiploid childhood B-cell precursor ALL: implications for leukemia biology and minimal residual disease analysis

Leukemia volume 23, pages 870–876 (2009)Cite this article

Abstract

Childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL) is generally a clonal disease in which the number of IGH rearrangements per cell does not exceed the number of the IGH alleles on chromosome 14. Consequently, monoclonal high hyperdiploid (HeH) cases with a trisomy 14 can harbor three rearrangements, a pattern that otherwise may be misinterpreted to be oligoclonal. Oligoclonal IGH rearrangements, on the other hand, may be instable at relapse and should therefore not be used for minimal residual disease analysis. We thus investigated the association between IGH allele copy numbers and the IGH rearrangement patterns in 90 HeH BCP ALL with either two (13%) or three copies (87%) of chromosome 14. HeH cases (44%) had an oligoclonal IGH rearrangement pattern, but true oligoclonality—after correction for the respective copy number of IGH alleles—was only 16%. Monoclonal and oligoclonal HeH cases had predominantly VH to preexisting DJH recombinations, a finding that contrasts with oligoclonal cases of other major genetic BCP ALL subgroups in which VH replacements prevail. We conclude that for the precise assessment and correct interpretation of clonality patterns in BCP ALL, the IGH allele copy number has to be taken into consideration.

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Acknowledgements

This study was supported by a grant from the OENB 12519 to Georg Mann and the St Anna Kinderkrebsforschung to E Renate Panzer-Grümayer. We thank Annemarie Wijkhuijs for technical support and Marion Zavadil for proofreading the paper.

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Author notes

  1. E Csinady, V H J van der Velden and R Joas: These authors contributed equally this work.

Authors and Affiliations

  1. Children's Cancer Research Institute, Vienna, Austria

    E Csinady, R Joas, S Fischer, M König, U Pötschger & E R Panzer-Grümayer

  2. Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

    V H J van der Velden, J F de Vries & J J M van Dongen

  3. Department of Clinical Genetics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

    H B Beverloo

  4. St Anna Kinderspital, Vienna, Austria

    G Mann, O A Haas & E R Panzer-Grümayer

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Correspondence to E R Panzer-Grümayer.

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Csinady, E., van der Velden, V., Joas, R. et al. Chromosome 14 copy number-dependent IGH gene rearrangement patterns in high hyperdiploid childhood B-cell precursor ALL: implications for leukemia biology and minimal residual disease analysis. Leukemia 23, 870–876 (2009). https://doi.org/10.1038/leu.2008.390

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