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T-ALL

Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL

Leukemia volume 19, pages 201–208 (2005)Cite this article

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is associated with chromosomal aberrations characterized by juxtaposition of proto-oncogenes to T-cell receptor gene loci (TCR), resulting in the deregulated transcription of these proto-oncogenes. Here, we describe the molecular characterization of a novel chromosomal aberration, inv(14)(q11.2q32.31), in a T-ALL sample, involving the recently described BCL11B gene and the TCRD locus. The inversion joined the 5′ part of BCL11B, including exons 1–3, to the TRDD3 gene segment of the TCRD locus, whereas the reciprocal breakpoint fused the TRDV1 gene segment to the fourth exon of BCL11B. The TRDV1-BCL11B joining region was 1344 bp long and contained fragments derived from 20q11.22, 3p21.33 and from 11p12, indicating the complex character of this aberration. A strong expression of in-frame transcripts with truncated BCL11B and TCRD constant region (TRDC) were observed, but in contrast to normal T cells and other T-ALL samples, no wild-type BCL11B transcripts were detected in the T-ALL sample. Screening of 37 other T-ALLs revealed one additional case with expression of the BCL11B-TRDC fusion transcript. As BCL11B appears to play a key role in T-cell differentiation, BCL11B disruption and disturbed expression may contribute to the development of T-cell malignancies in man.

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Acknowledgements

We gratefully acknowledge Kathrin Aßmus, Jeanette Bahr, Ingrid Wolvers-Tettero, Dorit Schuster and Claudia Becher for excellent technical assistance. We thank Dr M Dyer from the MRC Toxicology Unit/Leicester University, UK for valuable discussions. This work was supported by the Committee for Scientific Research, Poland (KBN 2 P05A 057 26; GKP), the Alfried Krupp von Bohlen und Halbach Stiftung (GKP and CAS), the German Josê Carreras Leukemia Foundation (GKP and CAS) the Dutch Cancer Society (EMCR 2002-2707, WAD, BV, JJM v D and AWL), the Haak Bastiaanse Kuneman Foundation (AWL), the Hensel Stiftung Kiel (RS) and the Deutsche Krebshilfe (RS and JIM-S).

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Authors and Affiliations

  1. Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland

    G K Przybylski

  2. Klinik für Innere Medizin C, Universität Greifswald, Sauerbruchstr., Greifswald, Germany

    G K Przybylski, J Wanzeck, P Grabarczyk, S Majunke, G Dölken & C A Schmidt

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

    W A Dik, B Verhaaf, J J M van Dongen & A W Langerak

  4. Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    J I Martin-Subero & R Siebert

  5. Robert-Rössle-Clinic, HELIOS Clinic Berlin-Buch, Charité, Berlin, Germany

    W-D Ludwig

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  1. G K Przybylski
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Correspondence to G K Przybylski.

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Przybylski, G., Dik, W., Wanzeck, J. et al. Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL. Leukemia 19, 201–208 (2005). https://doi.org/10.1038/sj.leu.2403619

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