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:

The sensitivity of human cells expressing RUNX1-RUNX1T1 to chemotherapeutic agents

Leukemia volume 20, pages 1883–1885 (2006)Cite this article

Taken together, these data suggest that expression of RUNX1-RUNX1T1 itself has no effect on the intrinsic susceptibility to cytotoxic chemicals. This raises the alternative hypothesis that RUNX1-RUNX1T1 moderates the influence of secondary abnormalities, which are required for RUNX1-RUNX1T1-expressing cells to undergo leukaemic transformation.8 For example, it is known that RUNX1-RUNX1T1 specifically upregulates the expression of γ-catenin in RUNX1-RUNX1T1-expressing cells and t(8;21) patients,7, 9 a protein that acts as a tumour suppressor gene in other contexts.

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
Figure 2

References

  1. Peterson LF, Zhang DE . The 8;21 translocation in leukemogenesis. Oncogene 2004; 23: 4255–4262.

    Article  CAS  Google Scholar 

  2. Tonks A, Tonks AJ, Pearn L, Pearce L, Hoy T, Couzens S et al. Expression of AML1-ETO in human myelomonocytic cells selectively inhibits granulocytic differentiation and promotes their self-renewal. Leukemia 2004; 18: 1238–1245.

    Article  CAS  Google Scholar 

  3. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood 1998; 92: 2322–2333.

    CAS  Google Scholar 

  4. Lutterbach B, Sun D, Schuetz J, Hiebert SW . The MYND motif is required for repression of basal transcription from the multidrug resistance 1 promoter by the t(8;21) fusion protein. Mol Cell Biol 1998; 18: 3604–3611.

    Article  CAS  Google Scholar 

  5. Pearson L, Leith CP, Duncan MH, Chen IM, McConnell T, Trinkaus K et al. Multidrug resistance-1 (MDR1) expression and functional dye/drug efflux is highly correlated with the t(8;21) chromosomal translocation in pediatric acute myeloid leukemia. Leukemia 1996; 10: 1274–1282.

    CAS  PubMed  Google Scholar 

  6. Schaich M, Harbich-Brutscher E, Pascheberg U, Mohr B, Soucek S, Ehninger G et al. Association of specific cytogenetic aberrations with mdr1 gene expression in adult myeloid leukemia and its implication in treatment outcome. Haematologica 2002; 87: 455–464.

    CAS  PubMed  Google Scholar 

  7. Tonks A, Pearn L, Musson M, Gilkes A, Mills K, Burnett A et al. RUNX1-RUNXIT1 induces over-expression of gamma-catenin in human CD34(+) cells, increasing self renewal and impairing granulocytic differentiation. Blood 2005; 106: 841A.

    Article  Google Scholar 

  8. Yuan Y, Zhou L, Miyamoto T, Iwasaki H, Harakawa N, Hetherington CJ et al. AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations. Proc Natl Acad Sci USA 2001; 98: 10398–10403.

    Article  CAS  Google Scholar 

  9. Muller-Tidow C, Steffen B, Cauvet T, Tickenbrock L, Ji P, Diederichs S et al. Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells. Mol Cell Biol 2004; 24: 2890–2904.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Amanda Gilkes and Megan Musson (Cardiff University) for their technical assistance in processing microarray samples. We are grateful to the MRC for access to patient sample material enrolled in the NCRI clinical trials. This work was supported by Leukaemia Research, UK.

Author information

Authors and Affiliations

  1. Department of Haematology, School of Medicine, Cardiff University, Cardiff, UK

    A Tonks, L Pearn, K I Mills, A K Burnett & R L Darley

Authors
  1. A Tonks
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L Pearn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K I Mills
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A K Burnett
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R L Darley
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tonks, A., Pearn, L., Mills, K. et al. The sensitivity of human cells expressing RUNX1-RUNX1T1 to chemotherapeutic agents. Leukemia 20, 1883–1885 (2006). https://doi.org/10.1038/sj.leu.2404364

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404364

Search

Advanced search

Quick links