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  • Oncogenomics
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Allelotype analysis in relapsed childhood acute lymphoblastic leukemia

Oncogene volume 22, pages 6970–6976 (2003)Cite this article

Abstract

We performed for the first time the allelotype of relapsed childhood acute lymphoblastic leukemia (ALL). A total of 38 cases were screened for loss of heterozygosity (LOH) using 71 markers. In all, 26 (68%) patients showed LOH on at least one chromosomal arm, indicating that LOH is a frequent event at relapse. The most frequent loss was found on chromosomal arm 9p at the p16/INK4a locus (39%). LOH at the TEL gene locus on chromosomal arm 12p also occurred often (25%). Frequent loss was observed on chromosome arms 4q (20%), 6q (21%), and 17q (20%). Sequential analysis (i.e. samples obtained from both initial diagnosis and relapse) shows that some patients (63%) have the identical LOH status at both phases, suggesting the presence of the same clone. Other samples (37%) showed distinct LOH alterations, indicating clonal evolution at relapse. Despite the heterogeneous and complex changes, some shared LOH loci occurred in these matched samples, suggesting that many of the same tumor-suppressor genes are aberrant at both phases. In summary, novel tumor-suppressor genes on chromosome arms 4q, 6q, and 17q, as well as the p16 and TEL genes, have an important role in the relapse of childhood ALL.

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Acknowledgements

We are grateful to Wolf Dieter Ludwig for providing the immunophenotypic data. We thank Ian K Williamson, Jeffrey Grewal, and Harry E Taub for technical help. We also thank the Board and the Clinicians of the Dutch Childhood Oncology Group for kindly providing ALL cell samples. This work was supported in part by grants from National Institutes of Health, C and H Koeffler Fund, Parker Hughes Trust, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Uehara Memorial Foundation, and Grant-in-Aid from the Ministry of Education, Culture Sports, Science, and Technology of Japan. HPK is a member of the Jonsson Comprehensive Cancer Center and the Molecular Biology Institute, and holds the endowed Mark Goodson Chair of Oncology Research at Cedars-Sinai Medical Center/UCLA School of Medicine.

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Authors and Affiliations

  1. Department of Medicine, Kochi Medical School, Okohcho, Nankoku, 783-8505, Kochi, Japan

    Seisho Takeuchi & Hiromi Seo

  2. Institute of Human Genetics, University of Heidelberg, Heidelberg, D-69120, Germany

    Taku Seriu & Claus R Bartram

  3. Department of Immunology, Erasmus University Rotterdam, Rotterdam, The Netherlands

    Jacques J M van Dongen & Tomasz Szczepański

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

    Tomasz Szczepański

  5. Division of Hematology/Oncology, Cedars-Sinai Research Institute, UCLA School of Medicine, Los Angeles, 90048, CA, USA

    Kunihiro Tsukasaki, Naoko Takeuchi, Anthony C Fermin & H Phillip Koeffler

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  1. Seisho Takeuchi
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  2. Taku Seriu
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Correspondence to Seisho Takeuchi.

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Takeuchi, S., Seriu, T., van Dongen, J. et al. Allelotype analysis in relapsed childhood acute lymphoblastic leukemia. Oncogene 22, 6970–6976 (2003). https://doi.org/10.1038/sj.onc.1206974

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