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TCRB gene rearrangements in childhood and adult precursor-B-ALL: frequency, applicability as MRD-PCR target, and stability between diagnosis and relapse

Leukemia volume 18, pages 1971–1980 (2004)Cite this article

Abstract

Using the multiplex PCR tubes of the BIOMED-2 Concerted Action, TCRB gene rearrangements were detected in 35% of childhood (n=161) and adult (n=172) precursor-B-ALL patients (Vβ–(Dβ)–Jβ in 25%; Dβ–Jβ in 15%). The presence of TCRB rearrangements showed a significant relation with age (highest frequency of 46% between 5 and 10 years of age) and the presence of TEL-AML1 transcripts, and was associated with relatively high frequencies of IGK-Kde, TCRG, and Vδ2-Jα rearrangements. In 62 out of 65 patients with Southern blot-detected Vβ–(Dβ)–Jβ and/or Dβ–Jβ rearrangements, at least one TCRB gene rearrangement was detected by PCR. Based on combined Southern blot and PCR analysis, oligoclonal TCRB gene rearrangements were observed in only 12% of patients. Analysis of paired diagnosis and relapse samples (n=26) showed that 20 out of 24 (83%) Vβ–(Dβ)–Jβ rearrangements and eight out of 14 (57%) Dβ–Jβ rearrangements remained stable. Using real-time quantitative PCR, a quantitative range ⩽10−4 was obtained in 64% of TCRB gene rearrangements and in 86% of cases a sensitivity ⩽10−4 was obtained. In conclusion, TCRB gene rearrangements occur in 35% of precursor-B-ALL patients and are relatively stable and sensitive PCR targets for detection of minimal residual disease, particularly if this concerns complete Vβ–(Dβ)–Jβ rearrangements.

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Acknowledgements

We gratefully acknowledge Bibi van Bodegom for secretarial assistance, Marieke Comans-Bitter for preparation of the figures, Sabine Hug and Regina Reutzel for providing clinical data, and Petra Chall, Petra Neumann, Frauke Hemken, and Heidrun Seppelt for their technical assistance. We thank Dr AW Langerak, Dr M van der Burg, and Dr MWJC Jansen for critically reviewing the manuscript. We thank the pediatric oncologists of the department of Pediatrics, Erasmus MC-Sophia, for the collection of samples at diagnosis and during follow-up. We acknowledge the Dutch Childhood Oncology Group and the German Multicenter ALL Study Group for kindly providing additional ALL cell samples. This study was supported by BIOMED-2 Concerted Action BMH4-CT98-3936 ‘PCR-based clonality studies for early diagnosis of lymphoproliferative disorders’, the Dutch Cancer Society/Koningin Wilhelmina Fonds (SNWLK 2000-2268), and the Wilhelm Sander-Stiftung (Grant 2001.074.1).

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Authors and Affiliations

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

    V H J van der Velden, P G Hoogeveen, M de Bie, P G Hart, T Szczepański & J J M van Dongen

  2. Medical Clinic II, University of Kiel, Germany

    M Brüggemann, T Raff, S Lüschen & M Kneba

  3. Department of Hematology, Medical Clinic III, University of Frankfurt, Germany

    H Pfeifer

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

    T Szczepański

  5. Dutch Childhood Oncology Group, The Hague, The Netherlands

    E R van Wering

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van der Velden, V., Brüggemann, M., Hoogeveen, P. et al. TCRB gene rearrangements in childhood and adult precursor-B-ALL: frequency, applicability as MRD-PCR target, and stability between diagnosis and relapse. Leukemia 18, 1971–1980 (2004). https://doi.org/10.1038/sj.leu.2403505

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