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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.

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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.

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  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.

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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

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  1. C Fegan
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  2. J Starczynski
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  4. C Pepper
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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

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