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Cytogenetics and molecular genetics of T-cell acute lymphoblastic leukemia: from thymocyte to lymphoblast

Leukemia volume 20, pages 1496–1510 (2006)Cite this article

Abstract

For long, T-cell acute lymphoblastic leukemia (T-ALL) remained in the shadow of precursor B-ALL because it was more seldom, and showed a normal karyotype in more than 50% of cases. The last decennia, intense research has been carried out on different fronts. On one side, development of normal thymocyte and its regulation mechanisms have been studied in multiple mouse models and subsequently validated. On the other side, molecular cytogenetics (fluorescence in situ hybridization) and mutation analysis revealed cytogenetically cryptic aberrations in almost all cases of T-ALL. Also, expression microarray analysis disclosed gene expression signatures that recapitulate specific stages of thymocyte development. Investigations are still very much actual, fed by the discovery of new genetic aberrations. In this review, we present a summary of the current cytogenetic changes associated with T-ALL. The genes deregulated by translocations or mutations appear to encode proteins that are also implicated in T-cell development, which prompted us to review the ‘normal’ and ‘leukemogenic’ functions of these transcription regulators. To conclude, we show that the paradigm of multistep leukemogenesis is very much applicable to T-ALL and that the different genetic insults collaborate to maintain self-renewal capacity, and induce proliferation and differentiation arrest of T-lymphoblasts. They also open perspectives for targeted therapies.

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Acknowledgements

This text presents research results of the Belgian programme on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister's Office, Science Policy Programming. The scientific responsibility is assumed by the authors. JC is a postdoctoral researcher, and PV is a clinical investigator of the ‘Fonds voor Wetenschappelijk Onderzoek Vlaanderen’.

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Authors and Affiliations

  1. Department of Hematology, Cliniques Universitaires St Luc, Catholic University of Louvain, Brussels, Belgium

    C Graux

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

    J Cools

  3. Center for Human Genetics, University of Leuven, Leuven, Belgium

    L Michaux, P Vandenberghe & A Hagemeijer

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  1. C Graux
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  2. J Cools
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  3. L Michaux
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Correspondence to A Hagemeijer.

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Graux, C., Cools, J., Michaux, L. et al. Cytogenetics and molecular genetics of T-cell acute lymphoblastic leukemia: from thymocyte to lymphoblast. Leukemia 20, 1496–1510 (2006). https://doi.org/10.1038/sj.leu.2404302

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