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Translocation t(14;18) is not associated with inferior outcome in chronic lymphocytic leukemia

Leukemia volume 23, pages 1201–1204 (2009)Cite this article

Translocations, in particular, unbalanced subtypes, were suggested to carry a poor prognostic effect in chronic lymphocytic leukemia (CLL).1, 2 Balanced translocations, especially those involving immunoglobulin (IG) genes, are recurrent, but uncommon, in this disorder.2, 3, 4 Their significance remains poorly understood.5 In published series,4, 6 part of the cases have unknown partner genes. Recurrent partner genes include BCL2, BCL3, BCL11A and CMYC. The best described is the t(14;19) involving the BCL3 gene, often associated with atypical morphology, unmutated VH genes and inferior prognosis.4, 6 The t(14;18)(q32;q21) and its variants, the t(2;18) (p11;q21) and t(18;22)(q21;q11), lead to overexpression of the anti-apoptotic bcl2 protein. It is interesting that, even in the absence of t(14;18), bcl2 overexpression is a constant finding in CLL, and is not explained by BCL2 gene hypomethylation. Other mechanisms, such as deletion or downregulation of miR–15a and miR–16–1, correlate inversely with bcl2 expression. Hence, the pathogenetic role, if any, of IGH/BCL2 translocations in disease initiation and evolution of CLL remains hypothetical.

In most studies, CLL cases with translocations involving IGH are analyzed as one group.3, 6 However, the target gene that becomes overexpressed as a result of the translocation may be relevant for the outcome. Here, the demographic features, clinical evolution, morphological and immunophenotypic characteristics of 40 consecutive patients, all showing an IG/BCL2 translocation, were analyzed as were the cytogenetic and molecular features. These patients were referred for cytogenetic characterization of CLL to the Centers for Human Genetics of the University Hospital Leuven, Gosselies (Belgium) and Le Kremlin–Bicêtre (France) between 1990 and 2008. Inclusion criteria were morphological diagnosis of B-CLL and typical immunophenotype, defined as a Matutes–Catovsky score ⩾3 and presence of t(14;18), t(2;18) or t(18;22) by conventional cytogenetics, fluorescent in situ hybridization (FISH) and/or molecular analysis. Clinical data were provided by the referring clinicians.

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Acknowledgements

We thank the following clinicians and clinical biologists for providing clinical data and material for morphological review: D Bauwens, T Braeckevelt, G Bries, D Brohée, C Chatelain, A Delannoy, A De Weweire, C Doyen, C Dubois, F Forget, O Hamdam, L Harlet, MF Louis, B Maes, S Marichal, P Mineur, S Neven, A Nijs, V Peeters, P Pierre, J Verschuere, L Waumans. We gratefully acknowledge D. Sartenaer, M. Stul and P. Vannuffel for excellent technical assistance and R Siebert for kindly providing probes for FISH. We also are indebted to A. Ferrant and A. Hagemeijer for critical reading of this manuscript. N Put is supported by Fonds voor Wetenschappelijk Onderzoek (FWO) Vlaanderen—Research Foundation Flanders. P Vandenberghe is a senior clinical investigator of FWO Vlaanderen.

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Authors and Affiliations

  1. Center for Human Genetics, Catholic University of Leuven, Leuven, Belgium

    N Put, P Meeus, I Wlodarska, P Vandenberghe & L Michaux

  2. Department of Clinical Biology, O.L.Vrouwziekenhuis, Aalst, Belgium

    P Meeus

  3. Department of Clinical Biology, University Hospital of Mont-Godinne, Yvoir, Belgium

    B Chatelain

  4. Center for Human Genetics, Institut de Pathologie, Gosselies, Belgium

    K Rack

  5. Department of Clinical Biology, University Hospital Leuven, Leuven, Belgium

    N Boeckx

  6. Department of Clinical Biology, AZ Sint-Jan AV, Brugge, Belgium

    F Nollet & A Van Hoof

  7. Department of Hematology, University Hospital of Mont-Godinne, Yvoir, Belgium

    C Graux

  8. Department of Hematology, University Hospital Saint-Luc, Brussels, Belgium

    E Van Den Neste

  9. Department of Hematology, University Hospital Leuven, Leuven, Belgium

    A Janssens

  10. Department of Hematology, Salvator Hospital, Hasselt, Belgium

    V Madoe

  11. Département de Cytogénétique, Laboratoire d'Hématologie, Le Kremlin-Bic, ê, tre, France

    C Bilhou-Nabera

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  1. N Put
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Correspondence to L Michaux.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Put, N., Meeus, P., Chatelain, B. et al. Translocation t(14;18) is not associated with inferior outcome in chronic lymphocytic leukemia. Leukemia 23, 1201–1204 (2009). https://doi.org/10.1038/leu.2009.44

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