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Comparative analysis of T-cell receptor gene rearrangements at diagnosis and relapse of T-cell acute lymphoblastic leukemia (T-ALL) shows high stability of clonal markers for monitoring of minimal residual disease and reveals the occurrence of second T-ALL

Leukemia volume 17, pages 2149–2156 (2003)Cite this article

Abstract

A total of 28 children and nine adults with relapsed T-ALL were analyzed for the configuration of their T-cell receptor (TCR) and TAL1 genes at diagnosis and relapse to evaluate their stability throughout the disease course. A total of 150 clonal TCR and TAL1 gene rearrangements were identified in the 37 patients at diagnosis. In 65% of cases all rearrangements and in 27% of cases most rearrangements found at diagnosis were preserved at relapse. Two children with unusually late T-ALL recurrences displayed completely different TCR gene rearrangement sequences between diagnosis and relapse. This indicates that a proportion of very late T-ALL recurrences might represent second T-ALL. Specifically, 88% of clonal rearrangements identified at diagnosis in truly relapsed T-ALL were preserved at relapse. This is significantly higher as compared to previously studied precursor-B-ALL (∼70%). Thus, from biological point of view, immunogenotype of T-ALL is more stable as compared with precursor-B-ALL. The overall stability of TCR gene rearrangements was higher in adult T-ALL (97%) than in childhood T-ALL (86%). Based on the stability of TCR gene rearrangements, we propose a strategy for PCR target selection (TCRD+TAL1 → TCRB → TCRG), which probably allows reliable minimal residual disease detection in all T-ALL patients.

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Acknowledgements

We are grateful to Professor Dr R Benner and Professor Dr D Sońta-Jakimczyk for their continuous support, and Mrs WM Comans-Bitter for preparation of the figures.

We thank the Board and the Clinicians of the Dutch Childhood Oncology Group for kindly providing T-ALL cell samples.

This study was supported by the Dutch Cancer Foundation/Koningin Wilhelmina Fonds (Grants SNWLK 97-1567 and SNWLK 2000-2268).

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Author notes

  1. M Kneba: Coordinator of the MRD-Detection Group of the ‘Kompetenznetz Leukämien’ and the German Multicenter Adult ALL-Study Group

Authors and Affiliations

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

    T Szczepański, V H J van der Velden, D C H Jacobs & J J M van Dongen

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

    T Szczepański

  3. II Medizinischer Klinik der Universität, Kiel, Germany

    T Raff, M Brüggemann & M Kneba

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

    E R van Wering

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Szczepański, T., Velden, V., Raff, T. et al. Comparative analysis of T-cell receptor gene rearrangements at diagnosis and relapse of T-cell acute lymphoblastic leukemia (T-ALL) shows high stability of clonal markers for monitoring of minimal residual disease and reveals the occurrence of second T-ALL. Leukemia 17, 2149–2156 (2003). https://doi.org/10.1038/sj.leu.2403081

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