Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

The role of the bax gene polymorphism G(−248)A in chronic lymphocytic leukemia

Leukemia volume 20, pages 1460–1461 (2006)Cite this article

Two recent publications in Leukemia have investigated the potential role of the bax G(−248)A polymorphism in chronic lymphocytic leukemia (CLL),1, 2 which pertain to our previous study,3 and that of Saxena et al.4 Our single centre study of 203 patients showed that this polymorphism significantly influenced Bax protein expression, overall survival (P=0.05) and in particular survival from first treatment (P=0.012). In contrast to the original paper by Saxena et al.4 we showed no difference in allele frequency between CLL samples and those derived from healthy volunteers, nor an increased incidence of the polymorphism in advanced stage disease. Unfortunately, Nuckel et al.2 misquote our work by stating that we showed an association between the polymorphism and advanced stage disease — we did not (P=0.62). In all other aspects, Nuckel et al.2 assessed clinical and prognostic parameters that we and Skogsberg et al.1 had previously identified as irrelevant with regards to the bax G(−248)A polymorphism. Crucially, they failed to address the pivotal question of the role of the polymorphism on therapeutic response.

Although many of the findings from the study of Skogsberg et al.1 (463 patients) and our own are compatible, there are a number of major differences. (1) They failed to identify any significant overall survival difference (median survival 85 months versus 102 months; P=0.21 in 350 patients) or survival from first treatment (median survival 36 months versus 63 months; P=0.26 in 98 patients). (2) They could not demonstrate a difference in bax RNA expression between the polymorphic groups. These differences between the two studies are worthy of further comment.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Skogsberg A, Tobin G, Krober A, Kienle D, Thunberg U, Aleskog A et al. The G(−248)A polymorphism in the promoter region of the bax gene does not correlate with prognostic markers or overall survival in chronic lymphocytic leukaemia. Leukemia 2006; 20: 77–81.

    Article  CAS  Google Scholar 

  2. Nuckel H, Frey UH, Sellman L, Bau M, Durig J, Durhsen U et al. Bax gene G(−248)A promoter polymorphism and chronic lymphocytic leukaemia: lack of association with incidence, disease stage and progression-free survival. Leukemia 2006; 20: 724.

    Article  CAS  Google Scholar 

  3. Starczynski J, Pepper C, Pratt G, Hooper L, Thomas A, Milligan D et al. Common polymorphism G(−248)A in the promoter region of the bax gene results in significantly shorter survival in patients with chronic lymphocytic leukemia once treatment is initiated. J Clin Oncol 2005; 23: 1514–1521.

    Article  CAS  Google Scholar 

  4. Saxena A, Moshynska O, Sankaran K, Viswanathan S, Sheridan DP . Association of a novel single nucleotide polymorphism, G(−248)A, in the 5′-UTR of BAX gene chronic lymphocytic with disease progression and treatment resistance. Cancer Lett 2002; 187: 199–205.

    Article  CAS  Google Scholar 

  5. Pepper C, Hoy T, Thomas A, Bentley DP . Chlorambucil resistance in B-cell chronic lymphocytic leukaemia is mediated through failed Bax induction and selection of high Bcl-2 expressing subclones. Br J Haematol 1999; 104: 581–588.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology, Wales School of Medicine, Cardiff University, Heath Park, Cardiff, UK

    C Fegan & C Pepper

  2. Department of Haematology, Heart of England NHS Trust, Bordesley Green East, Birmingham, UK

    J Starczynski & G Pratt

  3. Institute for Cancer Research, University of Birmingham, Vincent Drive, Birmingham, UK

    G Pratt

  4. Department of Haematology, Llandough Hospital, Penarth, Vale of Glamorgan, UK

    C Fegan

Authors
  1. C Fegan
    View author publications

    Search author on:PubMed Google Scholar

  2. J Starczynski
    View author publications

    Search author on:PubMed Google Scholar

  3. G Pratt
    View author publications

    Search author on:PubMed Google Scholar

  4. C Pepper
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fegan, C., Starczynski, J., Pratt, G. et al. The role of the bax gene polymorphism G(−248)A in chronic lymphocytic leukemia. Leukemia 20, 1460–1461 (2006). https://doi.org/10.1038/sj.leu.2404280

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.leu.2404280

This article is cited by

Search

Advanced search

Quick links