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:

Evaluation of WT1 expression in bone marrow vs peripheral blood samples of children with acute myeloid leukemia—impact on minimal residual disease detection

Leukemia volume 27, pages 1194–1196 (2013)Cite this article

Subjects

Wilms’ tumor gene 1 (WT1) is located on chromosome 11p13. As a zinc finger transcription factor, WT1 regulates expression of many target genes involved in regulation of cell cycle, proliferation, differentiation and apoptosis.1, 2 Overexpression of WT1 was found in majority of acute leukemias and other hematological malignancies. WT1 has, therefore, been intensively studied as a potential prognostic factor, marker for minimal residual disease (MRD) and target for immunotherapy (summarized in references1, 3, 4, 5).

In this report, we focus on the role of WT1 as a marker for monitoring of malignant cells in patients with childhood acute myeloid leukemia (AML). Many important studies proved the usefulness of WT1 for this purpose, showing that this gene provides a promising tool for residual disease detection. In general, these studies were based on the analysis of bone marrow (BM) samples,6, 7, 8 while only minority used peripheral blood (PB) as a source of leukemic cells.9, 10 Considering the fact, that the percentage of blasts can differ between BM and PB, one could assume that the choice of material for WT1 detection may influence the subsequent analysis. Nevertheless, no consensus has been made so far.

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

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

References

  1. Scharnhorst V, van der Eb AJ, Jochemsen AG . WT1 proteins: functions in growth and differentiation. Gene 2001; 273: 141–161.

    Article  CAS  PubMed  Google Scholar 

  2. Haber DA, Sohn RL, Buckler AJ, Pelletier J, Call KM, Housman DE . Alternative splicing and genomic structure of the Wilms tumor gene WT1. Proc Natl Acad Sci USA 1991; 88: 9618–9622.

    Article  CAS  PubMed  Google Scholar 

  3. Sugiyama H . Wilms' tumor gene WT1: its oncogenic function and clinical application. Int J Hematol 2001; 73: 177–187.

    Article  CAS  PubMed  Google Scholar 

  4. Wagner KD, Wagner N, Schedl A . The complex life of WT1. J Cell Sci 2003; 116 (Pt 9): 1653–1658.

    Article  CAS  PubMed  Google Scholar 

  5. Ariyaratana S, Loeb DM . The role of the Wilms tumour gene (WT1) in normal and malignant haematopoiesis. Expert Rev Mol Med 2007; 9: 1–17.

    Article  PubMed  Google Scholar 

  6. Trka J, Kalinova M, Hrusak O, Zuna J, Krejci O, Madzo J et al. Real-time quantitative PCR detection of WT1 gene expression in children with AML: prognostic significance, correlation with disease status and residual disease detection by flow cytometry. Leukemia 2002; 16: 1381–1389.

    Article  CAS  PubMed  Google Scholar 

  7. Willasch AM, Gruhn B, Coliva T, Kalinova M, Schneider G, Kreyenberg H et al. Standardization of WT1 mRNA quantitation for minimal residual disease monitoring in childhood AML and implications of WT1 gene mutations: a European multicenter study. Leukemia 2009; 23: 1472–1479.

    Article  CAS  PubMed  Google Scholar 

  8. Weisser M, Kern W, Rauhut S, Schoch C, Hiddemann W, Haferlach T et al. Prognostic impact of RT-PCR-based quantification of WT1 gene expression during MRD monitoring of acute myeloid leukemia. Leukemia 2005; 19: 1416–1423.

    Article  CAS  PubMed  Google Scholar 

  9. Cilloni D, Messa F, Arruga F, Defilippi I, Gottardi E, Fava M et al. Early prediction of treatment outcome in acute myeloid leukemia by measurement of WT1 transcript levels in peripheral blood samples collected after chemotherapy. Haematologica 2008; 93: 921–924.

    Article  PubMed  Google Scholar 

  10. Ommen HB, Nyvold CG, Braendstrup K, Andersen BL, Ommen IB, Hasle H et al. Relapse prediction in acute myeloid leukaemia patients in complete remission using WT1 as a molecular marker: development of a mathematical model to predict time from molecular to clinical relapse and define optimal sampling intervals. Br J Haematol 2008; 141: 782–791.

    Article  CAS  PubMed  Google Scholar 

  11. Kramarzova K, Stuchly J, Willasch A, Gruhn B, Schwarz J, Cermak J et al. Real-time PCR quantification of major Wilms' tumor gene 1 (WT1) isoforms in acute myeloid leukemia, their characteristic expression patterns and possible functional consequences. Leukemia 2012; 26: 2086–2095.

    Article  CAS  PubMed  Google Scholar 

  12. Boublikova L, Kalinova M, Ryan J, Quinn F, O'Marcaigh A, Smith O et al. Wilms' tumor gene 1 (WT1) expression in childhood acute lymphoblastic leukemia: a wide range of WT1 expression levels, its impact on prognosis and minimal residual disease monitoring. Leukemia 2006; 20: 254–263.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the project (Ministry of Health, Czech Rep) for conceptual development of research organisation 00064203 (University Hospital Motol, Prague, Czech Rep), UNCE204012 and the COST program (OC 09051). We would like to thank the staff of the participating Czech Pediatric Hematology (CPH) centers for cooperation. We also appreciated the help of Katerina Muzikova for the initial processing of some samples.

Author information

Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, CLIP—Childhood Leukemia Investigation Prague, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic

    K Kramarzova, L Boublikova, J Stary & J Trka

Authors
  1. K Kramarzova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L Boublikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Stary
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Trka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J Trka.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kramarzova, K., Boublikova, L., Stary, J. et al. Evaluation of WT1 expression in bone marrow vs peripheral blood samples of children with acute myeloid leukemia—impact on minimal residual disease detection. Leukemia 27, 1194–1196 (2013). https://doi.org/10.1038/leu.2012.291

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2012.291

Search

Advanced search

Quick links