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:

Imperfect correlation between p53 dysfunction and deletion of TP53 and ATM in chronic lymphocytic leukaemia

Leukemia volume 20, pages 737–740 (2006)Cite this article

Chromosomal analysis by fluorescence in situ hybridisation (FISH)1 and functional analysis of the ATM-p53 pathway2 each provide powerful prognostic information in chronic lymphocytic leukaemia (CLL), but the relationship between these prognostic factors has not previously been investigated. This is a matter of considerable interest as p53 and ATM (a positive regulator of p53) are encoded at loci (17p13 and 11q23, respectively) that frequently undergo mono-allelic deletion, whereas an extra copy of the gene encoding MDM2 (a negative regulator of p53) is present in cases with trisomy 12.3 To investigate the extent of correlation between these two biological variables, 191 cases of CLL were subjected to chromosomal and p53 functional analysis.

Chromosomal abnormalities were detected by FISH using probes corresponding to D13S25 (13q14), D12Z3 (centromeric region of chromosome 12), p53 (17p13) and either ATM or YAC 755b11 (11q23). For cases analysed at the Royal Marsden Hospital (n=47), a cutoff of 5% was established for deletions of D13S25, p53 and ATM, 2% for trisomy 12 and 10% for YAC 755b11. For cases analysed in Liverpool (n=144), a cutoff of 5% was used for each probe. The overall proportion of patients found to have del(17)(p13), del(11)(q23), trisomy 12 and del(13)(q14) was 15, 19, 16 and 51%, respectively. Thirty-seven patients (19%) had more than one of these FISH defects, whereas 47 cases (25%) had none. To simply analysis, each patient was assigned a single karyotype in accordance with the hierarchical prognostic model proposed by Dohner et al.,1 in which del(17)(p13), del(11)(q23), trisomy 12 and del(13)(q14) have a descending order of importance. The overall frequency of each hierarchical karyotype obtained in this way (denoted as 17p−, 11q−, +12, 13q− and normal) was 15, 17, 13, 31 and 25%, respectively.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2

References

  1. Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Eng J Med 2000; 343: 1910–1916.

    Article  CAS  Google Scholar 

  2. Lin K, Sherrington PD, Dennis M, Matrai Z, Cawley JC, Pettitt AR . Relationship between p53 dysfunction, CD38 expression, and IgV(H) mutation in chronic lymphocytic leukemia. Blood 2002; 100: 1404–1409.

    Article  CAS  Google Scholar 

  3. Stilgenbauer S, Bullinger L, Lichter P, Dohner H, the German CLL Study Group (GCLLSG). Genetics of chronic lymphocytic leukemia: genomic aberrations and VH gene mutation status in pathogenesis and clinical course. Leukemia 2002; 16: 993–1007.

    Article  CAS  Google Scholar 

  4. Carter A, Lin K, Sherrington PD, Pettitt AR . Detection of p53 dysfunction by flow cytometry in chronic lymphocytic leukaemia. Br J Haematol 2004; 127: 425–428.

    Article  CAS  Google Scholar 

  5. Pettitt AR, Sherrington PD, Stewart G, Cawley JC, Taylor AM, Stankovic T . p53 dysfunction in B-cell chronic lymphocytic leukemia: inactivation of ATM as an alternative to TP53 mutation. Blood 2001; 98: 814–822.

    Article  CAS  Google Scholar 

  6. Lin K, Manocha S, Harris RJ, Matrai Z, Sherrington PD, Pettitt AR . High frequency of p53 dysfunction and low level of VH mutation in chronic lymphocytic leukemia patients using the VH3–21 gene segment. Blood 2003; 102: 1145–1146.

    Article  CAS  Google Scholar 

  7. Thornton PD, Gruszka-Westwood AM, Hamoudi RA, Atkinson S, Kaczmarek P, Morilla RM et al. Characterisation of TP53 abnormalities in chronic lymphocytic leukaemia. Hematol J 2004; 5: 47–54.

    Article  CAS  Google Scholar 

  8. Schaffner C, Stilgenbauer S, Rappold GA, Dohner H, Lichter P . Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic lymphocytic leukemia. Blood 1999; 94: 748–753.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology, Royal Liverpool University Hospital, Liverpool, UK

    A Carter, K Lin, P D Sherrington & A R Pettitt

  2. Cheshire and Merseyside Genetics Laboratories, Liverpool Women's Hospital, Liverpool, UK

    M Atherton, K Pearson & A Douglas

  3. Section of Haemato-oncology, Institute of Cancer Research, Sutton, Surrey, UK

    A Burford, V Brito-Babapulle, E Matutes & D Catovsky

Authors
  1. A Carter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P D Sherrington
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Atherton
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K Pearson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Douglas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A Burford
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. V Brito-Babapulle
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E Matutes
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. D Catovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. A R Pettitt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A R Pettitt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carter, A., Lin, K., Sherrington, P. et al. Imperfect correlation between p53 dysfunction and deletion of TP53 and ATM in chronic lymphocytic leukaemia. Leukemia 20, 737–740 (2006). https://doi.org/10.1038/sj.leu.2404120

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404120

This article is cited by

Search

Advanced search

Quick links