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Fusion GenesTEL-AML 1: Correlation with Ig-TCR genes

High incidence and unique features of antigen receptor gene rearrangements in TEL–AML1-positive leukemias

Leukemia volume 18, pages 84–91 (2004)Cite this article

Abstract

The t(12;21) translocation resulting in the TEL–AML1 gene fusion is found in 25% of childhood B-cell precursor (BCP) acute lymphoblastic leukemias (ALL). Since TEL–AML1 has been reported to induce cell cycle retardation and thus may influence somatic recombination, we analyzed 214 TEL–AML1-positive ALL by PCR for rearrangements of the immunoglobulin (Ig) and T-cell receptor (TCR) genes. As a control group, 174 childhood BCP ALL without a TEL–AML1 were used. The majority of TEL–AML1-positive leukemias had a higher number of Ig/TCR rearrangements than control ALL. They also had a more mature immunogenotype characterized by their high frequency of complete IGH, IGK-Kde, and TCRG rearrangements. While IGK-Kde and TCRG were more frequently rearranged on both alleles at higher age, IGH and TCRD rearrangements decreased in their incidence along with a decrease in biallelic IGH rearrangements. This suggests that the recombination process continues in these leukemias leading to ongoing rearrangements and possibly also deletions of antigen receptor genes. We here provide first evidence that somatic recombination of antigen receptor genes is affected by the TEL–AML1 fusion, and that further age-related differences are probably caused by the longer latency period of the prenatally initiated TEL–AML1-positive leukemias in older children.

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Acknowledgements

We thank Uli Monschein, Lilia Corral, Elisabetta d'Aniello, Simona Songia, Monica Spinelli, Giuseppe Germano, Laura DelGiudice, Annemarie Wijkhuijs, Simone Busenbender, Ivonne Gonnissen, Carmen Holzschuh, Heike Knappenschneider, Kirsten Linsmeier, Nicola Passow, and Cornelia Rütz for their excellent technical assistance, and Christos Diakos for fruitful discussions. The study was performed using the network of the Biology group within the I-BFM group. This study was supported by a grant from the Fonds zur Förderung Wissenschaftlicher Forschung (FWF P-13575-MED), by the Österreichische Kinderkrebshilfe, by the Fondazione MTettamanti, Fondazione Cariplo, Fondazione “Città della speranza”, Associazione Italiana per la Ricerca sul Cancro (AIRC), CNR-MIUR Progetto Finalizzato Oncologia, by a grant from the Deutsche Krebshilfe, and by the Dutch Cancer Society/Koningin Wilhelmina Fonds (Grants SNWLK 97-1567 and SNWLK 2000-2268).

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Authors and Affiliations

  1. Children's Cancer Research Institute, St Anna Kinderspital, Vienna, Austria

    S Hübner, M Konrad, U Pötschger & E R Panzer-Grümayer

  2. Centro Ricerca Tettamanti, Clinica Pediatrica Univ. Milano Bicocca, Ospedale San Gerardo, Monza, Italy

    G Cazzaniga & A Biondi

  3. Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany

    T Flohr & C R Bartram

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

    V H J van der Velden & J J M van Dongen

  5. Dipartimento di Pediatria, Laboratorio di Emato-Oncologia, Università di Padova, Padova, Italy

    G Basso

  6. Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany

    M Schrappe

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Hübner, S., Cazzaniga, G., Flohr, T. et al. High incidence and unique features of antigen receptor gene rearrangements in TEL–AML1-positive leukemias. Leukemia 18, 84–91 (2004). https://doi.org/10.1038/sj.leu.2403182

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Keywords

  • acute lymphoblastic leukemia
  • TEL–AML1
  • Ig/TCR rearrangements
  • PCR

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