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T Cell ALL

T cell receptor gamma (TCRG) gene rearrangements in T cell acute lymphoblastic leukemia reflect ‘end-stage’ recombinations: implications for minimal residual disease monitoring

Leukemia volume 14, pages 1208–1214 (2000)Cite this article

Abstract

The T cell receptor gamma (TCRG) gene configuration was established in a large series of 126 T cell acute lymphoblastic leukemia (T-ALL) patients using combined Southern blotting (SB) and heteroduplex PCR analyses. The vast majority of T-ALL (96%) displayed clonal TCRG gene rearrangements, with biallelic recombination in 91% of patients. A small immature subgroup of CD3− T-ALL (n = 5) had both TCRG genes in germline configuration, three of them having also germline TCRD genes. In five patients (4%) combined SB and PCR results indicated oligoclonality. In five rearrangements detected by SB, the Vγ gene segment could not be identified suggesting illegitimate recombination. Altogether, 83% of TCRG gene rearrangements involved either the most upstream Vγ2 gene (including four cases with interstitial deletion of 170 bp in Vγ2) and/or the most downstream Jγ2.3 segment, which can be perceived as ‘end-stage’ recombinations. Comparative analysis of the TCRG gene configuration in the major immunophenotypic subgroups indicated that TCRγδ+ T-ALL display a less mature immunogenotype as compared to TCRαβ+ and most CD3− cases. This was reflected by a significantly increased usage of the more downstream Vγ genes and the upstream Jγ1 segments. Comparison between adult and pediatric T-ALL patients did not show any obvious differences in TCRG gene configuration. The high frequency, easy detectability, rare oligoclonality, and frequent ‘end-stage’ recombinations make TCRG gene rearrangements principal targets for PCR-based detection of minimal residual disease (MRD) in T-ALL. We propose a simple heteroduplex PCR strategy, applying five primer combinations, which results in the detection of approximately 95% of all clonal TCRG gene rearrangements in T-ALL. This approach enables identification of at least one TCRG target for MRD monitoring in 95% of patients, and even two targets in 84% of T-ALL.

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Acknowledgements

We thank Drs K Hählen, IM Appel, RM Egeler, FGAJ Hakvoort-Cammel, WJD Hofhuis, GE van Zanen, B Löwenberg, P Sonneveld, GJ Ossenkoppele, GJ Schuurhuis, G Verhoef, Ph Vandekerckhove, M Stul, EJ Petersen, AW Dekker, D Campana, JC Kluin-Nelemans, W-D Ludwig, CE van der Schoot, and the Dutch Childhood Leukemia Study Group (DCLSG) for kindly providing T-ALL cell samples. Board members of the DCLSG are IM Appel, H van den Berg, JPM Bökkerink, MCA Bruin, JJ Groot-Loonen, SSN de Graaf, K Hählen, PM Hoogerbrugge, WA Kamps, FAE Nabben, JA Rammeloo, T Revesz, AYN Schouten-van Meeteren, AJP Veerman, M van Weel-Sipman, and RS Weening.

We are grateful to Prof dr R Benner, and Prof dr D Sońta-Jakimczyk for their continuous support, Dr EJ Moreau for sharing experimental data, and Mr TM van Os for preparation of the figures.

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Authors and Affiliations

  1. Department of Immunology, University Hospital Rotterdam/Erasmus University Rotterdam, Rotterdam, The Netherlands

    T Szczepański, AW Langerak, MJ Willemse, ILM Wolvers-Tettero & JJM van Dongen

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

    T Szczepański

  3. Dutch Childhood Leukemia Study Group, The Hague, The Netherlands

    ER van Wering

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Szczepański, T., Langerak, A., Willemse, M. et al. T cell receptor gamma (TCRG) gene rearrangements in T cell acute lymphoblastic leukemia reflect ‘end-stage’ recombinations: implications for minimal residual disease monitoring. Leukemia 14, 1208–1214 (2000). https://doi.org/10.1038/sj.leu.2401765

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