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Cytogenetics and Molecular Genetics

Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRβ-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique

Leukemia volume 21, pages 121–128 (2007)Cite this article

Abstract

Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRβ) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCRβ-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCRβ-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCRβ-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRβ-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRβ-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRβ-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.

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Acknowledgements

This study was supported by the Fonds voor Wetenschappelijk Onderzoek (FWO-) Vlaanderen, Grants G.0106.05 and GOA, grant no.12051203. This paper presents research results of the Belgian program of Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister's Office, Science Policy Programming. The scientific responsibility is assumed by the authors. BC is supported by the Belgian program of Interuniversity Poles of Attraction. NVR is a Postdoctoral fellow and BV is a Senior Clinical Investigator funded by the FWO-Vlaanderen. We are thankful to Betty Emanuel and Nurten Yigit for excellent technical assistance.

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Authors and Affiliations

  1. Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium

    B Cauwelier, B Poppe, N Van Roy, A D Paepe & F Speleman

  2. Laboratoire de Biochimie Génétique, Hôpital Robert Debré, Paris, France

    H Cavé & C Chalas

  3. Laboratoire d’Hématologie, CHU Strasbourg, Strasbourg, France

    C Gervais, M Lessard & L Mauvieux

  4. CHU Bretonneau, Tours, France

    C Barin & E Clappier

  5. CHU Saint-Antoine, Paris, France

    C Perot & J Van den Akker

  6. CHU Dijon, Dijon, France

    F Mugneret

  7. Hôpital Edouard Herriot, Lyon, France

    C Charrin & M P Pagès

  8. CHU Nancy, Nancy, France

    M-J Grégoire & P Jonveaux

  9. Institut Paoli-Calmettes, Marseille, France

    M Lafage-Pochitaloff & M J Mozzicconacci

  10. CHU Versailles, Versailles, France

    C Terré

  11. CHU Reims, Reims, France

    I Luquet & P Cornillet-Lefebvre

  12. Hôpital Robert Debré, Paris, France

    B Laurence

  13. CHU Clémenceau, Caen, France

    G Plessis

  14. INSERM E353, CHU de Grenoble, France

    C Lefebvre & D Leroux

  15. Centre for Medical Genetics, Hôpital UCL-StLuc, Brussels, Belgium

    H Antoine-Poirel

  16. Hematology Laboratory and INSERM U728, Institut Universitaire d’ Hématologie, Hôpital Saint-Louis, Paris, France

    C Graux, F Sigaux & J Soulier

  17. Department of Medical Genetics, University Hospital Erasme, Brussels, Belgium

    P Heimann

  18. Department of Clinical Chemistry, Microbiology and Immunology, Centre for Molecular Diagnostics, Ghent University Hospital, Ghent, Belgium

    B Verhasselt

  19. Department of Pediatric Hematology/Oncology, Ghent University Hospital, Ghent, Belgium

    Y Benoit & B D Moerloose

  20. Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, Leuven, Belgium

    K D Keersmaecker & J Cools

  21. Centre for Human Genetics, University of Leuven, Leuven, Belgium

    A Hagemeijer

  22. Laboratoire d’Hématologie, Hôpital Purpan, Toulouse, France

    N Dastugue

  23. INSERM EMI0210, Hôpital Necker-Enfants Malades, Paris, France

    R Berger

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  1. B Cauwelier
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  2. H Cavé
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Correspondence to F Speleman.

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Cauwelier, B., Cavé, H., Gervais, C. et al. Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRβ-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique. Leukemia 21, 121–128 (2007). https://doi.org/10.1038/sj.leu.2404410

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