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Expression of the two alternative [a] and [b] transcripts of CCND1 gene in cyclin D1-expressing B-malignancies: relevance for the pathogenesis

Leukemia volume 17, pages 652–655 (2003)Cite this article

TO THE EDITOR

In normal B-lymphoid cells, whatever the stage of differentiation, the CCND1 gene is silent. By contrast, in some hematological B-malignancies such as MCL, HCL and MM, the CCND1 gene is activated and leads to the expression of cyclin D1 mRNA and protein. In this study, we have examined the presence of the alternative cyclin D1 transcript referred to as form [b] in cells isolated from MCL, HCL patients and MM cell lines and investigated the presence of the corresponding protein. By direct or seminested RT-PCR, we have demonstrated that cyclin D1 transcript form [b] is present in all tumoral cells expressing cyclin D1 form [a] irrespectively of the presence of t(11;14)(q13;q32). Then, the generation of an alternative splice does not depend on the mechanism of CCND1 gene activation. The alternative splice form [b] is generated by an A/G polymorphism within the splice donor sequence at position 870,2 but both alleles can splice to form both [a] and [b] transcripts. Whatever the mechanism of CCND1 gene activation, the cyclin D1 open reading frame as well as the upstream regulatory sequences remain intact; thus, the presence of transcripts [a] and [b] depends only on the A/G polymorphism. We cannot exclude that form [b] transcript could play a role by itself, but our data support the notion that the cyclin D1 protein form [b] does not participate in the transformation process in mature B-cell malignancies. In good agreement with us, a recent report has evaluated the impact of the A/G polymorphism on the survival of a group of MCL patients and found no significant influence.8

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References

  1. Inaba T, Matsushime H, Valentine M, Roussel MF, Sherr CJ, Look AT . Genomic organization, chromosomal localization, and independent expression of human cyclin D genes. Genomics 1992; 13: 565–574.

    Article  CAS  Google Scholar 

  2. Betticher DC, Thatcher N, Altermatt HJ, Hoban P, Ryder WD, Heighway J . Alternate splicing produces a novel cyclin D1 transcript. Oncogene 1995; 11: 1005–1011.

    CAS  PubMed  Google Scholar 

  3. Hosokawa Y, Joh T, Maeda Y, Arnold A, Seto M . Cyclin D1/PRAD1/BCL-1 alternative transcript [B] protein product in B-lymphoid malignancies with t(11;14)(q13;q32) translocation. Int J Cancer 1999; 81: 616–619.

    Article  CAS  Google Scholar 

  4. Troussard X, Avet-Loiseau H, Macro M, Mellerin M, Malet M, Roussel M, Sola B . Cyclin D1 expression in patients with multiple myeloma. Hematol J 2000; 1: 181–185.

    Article  CAS  Google Scholar 

  5. Duquesne F, Florent M, Roué G, Troussard X, Sola B . Ectopic expression of cyclin D1 impairs the proliferation and enhances the apoptosis of a murine lymphoid cell line. Cell Death Differ 2001; 8: 51–62.

    Article  CAS  Google Scholar 

  6. de Boer CJ, Schuuring E, Dreef E, Peters G, Bartek J, Kluin PM, van Krieken JH . Cyclin D1 protein analysis in the diagnosis of mantle cell lymphoma. Blood 1995; 86: 2715–2723.

    CAS  Google Scholar 

  7. Sawa H, Ohshima TA, Ukita H, Murakami H, Chiba Y, Kamada H, Hara M, Saito I . Alternatively spliced forms of cyclin D1 modulate entry into the cell cycle in an inverse manner. Oncogene 1998; 16: 1701–1712.

    Article  CAS  Google Scholar 

  8. Howe D, Lynas C . The cyclin D1 alternative transcripts [a] and [b] are expressed in normal and malignant lymphocytes and their relative levels are influenced by the polymorphism at codon 241. Haematologica 2001; 86: 563–569.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. UPRES-EA 2128, UFR de Médecine, Caen, France

    G Roué, S Krieger, M Florent, M Roussel, F Duquesne, X Troussard & B Sola

  2. Laboratoire d'Hématologie, CHU Côte de Nacre, Caen, France

    X Troussard

  3. Laboratoire de Microbiologie de l'Environnement, EA-956 USC INRA, Caen, France

    V Pichereau

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  1. G Roué
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  2. S Krieger
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Roué, G., Krieger, S., Florent, M. et al. Expression of the two alternative [a] and [b] transcripts of CCND1 gene in cyclin D1-expressing B-malignancies: relevance for the pathogenesis. Leukemia 17, 652–655 (2003). https://doi.org/10.1038/sj.leu.2402817

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