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Prediction of immunophenotype, treatment response, and relapse in childhood acute lymphoblastic leukemia using DNA microarrays

Leukemia volume 18, pages 1270–1277 (2004)Cite this article

Abstract

Gene expression profiling is a promising tool for classification of pediatric acute lymphoblastic leukemia (ALL). We analyzed the gene expression at the time of diagnosis for 45 Danish children with ALL. The prediction of 5-year event-free survival or relapse after treatment by NOPHO-ALL92 or 2000 protocols resulted in a classification accuracy of 78% and a Matthew's correlation coefficient of 0.59 independently of immunophenotypes. The sensitivity and specificity for prediction of relapse were 87% and 69% respectively. Prediction of high vs low levels of the minimal residual disease (MRD) on day 29 (⩾0.1% or ⩽0.01%) resulted in an accuracy of 100% for precursor-B samples. The classification accuracy of precursor-B- vs T-lineage immunophenotypes was 100% even in samples with as little as 10% leukemic blast cells, and the immunophenotype classifier constructed in this study was able to classify 131 of 132 samples from a previous study correctly. Our study indicates that the Affymetrix Focus Array GeneChip may be used without loss of classification performance compared to previous studies using the far more extensive U133A+B GeneChip set. Further studies should focus on prediction of MRD, as this prediction would relate strongly to long-term outcome and could thus determine the intensity of induction therapy.

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Acknowledgements

We thank staff members from the Section of Clinical Hematology and Oncology, Rigshospitalet, laboratory technicians from the Department of Clinical Immunology, Rigshospitalet and people at Center for Biological Sequence Analysis, Technical University of Denmark for their assistance. This work was supported financially by Knud Veilskov's Foundation, Ellen and Aage Fausbølls Health Foundation of 1975, Holger and Inez Petersens Foundation, Gangsted Foundation, Vilhelm Pedersens Foundation, Danish National Research Foundation, Danish Biotechnology Instrument Centre, Danish Center for Scientific Computing, Novo Nordisk, Novozymes, Carlsberg Foundation, The Danish Cancer Society (Grant Nos. 99 144 10 9132, 94-100-28, and 96-100-07), The Danish Cancer League, The Edith & Søren Kiilerich Hansen Family Foundation, The Emil and Inger Hertz Foundation, The Kornerup Foundation, The Lundbeck Foundation, The Medical Research Council in Denmark (Grant No. 9401011), and The Queen Louise's Children's Hospital Foundation.

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  1. H Willenbrock and A S Juncker: These two authors contributed equally to this work

Authors and Affiliations

  1. Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark

    H Willenbrock, A S Juncker & S Knudsen

  2. The Pediatric Clinic II, The University Hospital, Rigshospitalet, Copenhagen, Denmark

    K Schmiegelow

  3. Department of Clinical Immunology, Tissue Typing Laboratory, The University Hospital, Rigshospitalet, Copenhagen, Denmark

    L P Ryder

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  1. H Willenbrock
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  2. A S Juncker
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  4. S Knudsen
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  5. L P Ryder
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Correspondence to S Knudsen.

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Willenbrock, H., Juncker, A., Schmiegelow, K. et al. Prediction of immunophenotype, treatment response, and relapse in childhood acute lymphoblastic leukemia using DNA microarrays. Leukemia 18, 1270–1277 (2004). https://doi.org/10.1038/sj.leu.2403392

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