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Chronic Lymphocytic Leukemia

The BCL-2 promoter (−938C>A) polymorphism does not predict clinical outcome in chronic lymphocytic leukemia

Leukemia volume 22, pages 339–343 (2008)Cite this article

Abstract

The (−938C>A) polymorphism in the promoter region of the BCL-2 gene was recently associated with inferior time to treatment and overall survival in B-cell chronic lymphocytic leukemia (CLL) patients displaying the −938A/A genotype and may thus serve as an unfavorable genetic marker in CLL. Furthermore, the −938A/A genotype was associated with increased expression of Bcl-2. To investigate this further, we analyzed the −938 genotypes of the BCL-2 gene in 268 CLL patients and correlated data with treatment status, overall survival and known prognostic factors, for example, Binet stage, immunoglobulin heavy-chain variable (IGHV) mutational status and CD38 expression. In contrast to the recent report, the current cohort of CLL patients showed no differences either in time to treatment or overall survival in relation to usage of a particular genotype. In addition, no correlation was evident between the (−938C>A) genotypes and IGHV mutational status, Binet stage or CD38. Furthermore, the polymorphism did not appear to affect the Bcl-2 expression at the RNA level. Taken together, our data do not support the use of the (−938C>A) BCL-2 polymorphism as a prognostic marker in CLL and argue against its postulated role in modulating Bcl-2 levels.

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Acknowledgements

This study was supported by grants from the Swedish Cancer Society, The Lion's Cancer Research Foundation, Uppsala, and the Swedish Society for Medical Research. We thank Juhani Vilpo for providing data concerning the patients treated in Tampere, Finland. The SNP genotyping was performed by the SNP Technology Platform, Department of Medical Sciences, Uppsala University (www.genotyping.se). We are grateful to Dr Mattias Jansson and Lesley Sutton for their technical advice and assistance in this study.

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Authors and Affiliations

  1. Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden

    M A Kaderi, M Norberg, F Murray, C Sundström, G Tobin & R Rosenquist

  2. Department of Medicine at Karolinska University Hospital, Huddinge, Sweden

    M Merup

  3. Department of Medical Biosciences, Pathology, Umeå University, Sweden

    G Roos

  4. Department of Medical Sciences, Uppsala University, Uppsala, Sweden

    A Åleskog & T Axelsson

  5. Department of Hematology, Lund University Hospital, Lund, Sweden

    K Karlsson

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  1. M A Kaderi
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Correspondence to R Rosenquist.

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Kaderi, M., Norberg, M., Murray, F. et al. The BCL-2 promoter (−938C>A) polymorphism does not predict clinical outcome in chronic lymphocytic leukemia. Leukemia 22, 339–343 (2008). https://doi.org/10.1038/sj.leu.2405042

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