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T-Leukemias

Cyclin D2 dysregulation by chromosomal translocations to TCR loci in T-cell acute lymphoblastic leukemias

Leukemia volume 20, pages 82–86 (2006)Cite this article

Abstract

Strong expression of at least one of the three D-type cyclins is common in human cancers. While the cyclin D1 and D3 genes (CCND1 and CCND3) are recurrently involved in genomic rearrangements, especially in B-cell lymphoid neoplasias, no clear involvement of the cyclin D2 gene (CCND2) has been reported to date. Here, we identified chromosomal translocations targeting the CCND2 locus at 12p13, and the T-cell receptor beta (TCRB) or the TCRA/D loci in T-cell acute lymphoblastic leukemias (T-ALLs). Expression analysis demonstrated dramatic cyclin D2 overexpression in the translocated cases (n=3) compared to other T-ALLs (total, n=89). In order to evaluate dysregulation in T-ALL with respect to normal T-cell differentiation, we analyzed CCND2 expression in normal purified human thymic subpopulations. CCND2 levels were downregulated through progression from the early stages of human T-cell differentiation, further suggesting that the massive and sustained expression in the CCND2-rearranged T-ALL cases was oncogenic. Association with other oncogene expression (TAL1, HOXAs, or TLX3/HOX11L2), NOTCH1 activating mutations, and/or CDKN2A/p16/ARF deletion, showed that cyclin D2 dysregulation could contribute to multi-event oncogenesis in various T-ALL groups. This report is the first clear evidence of a direct involvement of cyclin D2 in human cancer due to recurrent somatic genetic alterations.

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Acknowledgements

This work was supported from INSERM and Paris 7 University, and by a grant from the Ligue Nationale contre le Cancer (‘Programme Cartes d’Identité des Tumeurs’). We thank the FAB members Marie-Thérèse Daniel and Georges Flandrin for expert morphological evaluation of leukemic samples, and Karine Chemin, Armelle Regnault, Marie-Luisa Toribio and Alain Aurias for helpful contributions and comments. We are grateful to Jean-Christophe Bories, Josée Hebert, and Hugues de Thé for critical reading of the manuscript.

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Authors and Affiliations

  1. Genome Rearrangements and Cancer Group, INSERM U728 and Institut Universitaire d’Hematologie, Hôpital Saint-Louis and Paris 7 University, Paris, France

    E Clappier, W Cuccuini, J-M Cayuela, D Vecchione, A Baruchel, H Dombret, F Sigaux & J Soulier

  2. Hematology Laboratory, Hôpital Saint-Louis, Paris, France

    E Clappier, W Cuccuini, J-M Cayuela, F Sigaux & J Soulier

  3. Pediatric Hematology Department, Hôpital Saint-Louis, Paris, France

    A Baruchel

  4. Adult Hematology Department, Hôpital Saint-Louis, Paris, France

    H Dombret

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  1. E Clappier
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Correspondence to J Soulier.

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Clappier, E., Cuccuini, W., Cayuela, JM. et al. Cyclin D2 dysregulation by chromosomal translocations to TCR loci in T-cell acute lymphoblastic leukemias. Leukemia 20, 82–86 (2006). https://doi.org/10.1038/sj.leu.2404008

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