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Detection of p53 dysfunction in chronic lymphocytic leukaemia cells through multiplex quantification of p53 target gene induction

Leukemia volume 23, pages 1352–1355 (2009)Cite this article

Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease with a variable clinical course. Deletions of the long arm of chromosome 11 (11q-) and especially the short arm of chromosome 17 (17p-) are the strongest independent prognostic factors associated with an adverse outcome.1 17p- corresponds to allelic loss of the tumour suppressor gene, p53, whereas 11q- implies loss of the ataxia telangiectasia (ATM) gene, an upstream mediator in the p53 signalling pathway, and both are associated with dysfunction of the p53 tumour suppressor pathway.2 These chromosomal abnormalities may play an important role in relapse on therapy, as the prevalence of 17p- and 11q- increases from 5–15% at diagnosis to over 50% during relapse.3 Currently, fluorescence in situ hybridisation (FISH) is a widely used technique to detect chromosomal anomalies in cancer samples. Although recent studies show that deletions of one p53 or ATM alleles are frequently accompanied by mutation of the other allele, the exact overlap between the patient populations defined by such deletions and p53 dysfunction remains poorly defined. It would therefore be clinically relevant to test the activity of the p53 pathway in a functional assay, in addition to FISH analysis.

Measuring p53 and/or p21 protein levels by western blot (WB) following ionising radiation (IR) is an accepted semi-quantitative method to detect p53 (dys)function in tumour samples.2, 4 Alternative techniques have also been described, such as flow-cytometric staining of the cell-surface receptor CD954 or intracellular staining of p53 and p215 after IR, and Functional Analysis of Separated Alleles in Yeast (FASAY).6 Earlier, we have evaluated the apoptosis gene profile of CLL samples after fludarabine incubation through reverse transcriptase-multiplex ligation-dependent probe amplification (RT-MLPA) analysis, and observed that induction of expression of the p53 responsive gene, Puma strictly relied on functional p53.7

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Acknowledgements

Arnon P Kater is supported by a ‘Veni’ grant from ZonMw (The Netherlands Organization for Health Research and Development). We thank Ronald van Ree for critical reading of the paper and comments.

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Authors and Affiliations

  1. Department of Haematology, Academic Medical Centre, Amsterdam, The Netherlands

    R Mous, A Jaspers, D M P Luijks, M H J van Oers & A P Kater

  2. Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands

    C H M Mellink

  3. Department of Experimental Immunology, Academic Medical Centre, Amsterdam, The Netherlands

    E Eldering

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  1. R Mous
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Correspondence to E Eldering.

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Mous, R., Jaspers, A., Luijks, D. et al. Detection of p53 dysfunction in chronic lymphocytic leukaemia cells through multiplex quantification of p53 target gene induction. Leukemia 23, 1352–1355 (2009). https://doi.org/10.1038/leu.2009.71

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