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:

Therapy-related acute myeloid leukaemia with t(8;16)(p11;p13);MOZ-CBP and polymorphisms in detoxifying and DNA repair genes

Leukemia volume 23, pages 1164–1167 (2009)Cite this article

Access through your institution
Buy or subscribe

Therapeutic advances over the last 20 years have led to an improved survival of patients with solid tumours, some being cured of their disease. However, an unwelcome consequence of this success has been an increase in the incidence of secondary malignancies.1, 2, 3 Therapy-related myeloid neoplasms, including therapy-related acute myeloid leukaemia (t-AML) and therapy-related myelodysplasia, can occur in patients after therapy for both solid tumours and haematological malignancies.3, 4 The cumulative risk of t-AML at 10 years after treatment for breast cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma and ovarian cancer, for example, has been estimated as 1.5, 3.8, 7.9 and 8.5%, respectively.4 Commonly described risk factors for t-AML include the use of alkylating agents, topoisomerase II inhibitors and radiotherapy. Both the incidence and the latent period between primary therapy and therapy-related myelodysplasia or t-AML are dependent on the drug type administered, dose intensity and cumulative dose.3, 5, 6

The risk of t-AML may also, in part, be due to inherited genetic factors.2 These factors include polymorphisms within genes encoding detoxifying enzymes, such as members of the P450 protein family (CYP1A1), the quinone oxidoreductase enzyme (NQO1) and members of the glutathione S-transferase (GST) family, and polymorphisms within genes encoding DNA repair enzymes.2 Detoxifying enzymes comprise two main groups. The first or phase I enzymes, such as Cytochrome P450s, yield highly reactive metabolites, which are subsequently detoxified and metabolized by the second or phase II enzymes, such as NQO1 and GSTs.2, 7 DNA repair enzymes such as RAD51, XPD and XRCC3 are required to maintain genetic integrity and stability. Polymorphisms in the genes encoding either of these types of enzymes have been reported to increase susceptibility to a number of malignancies.

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Figure 1

References

  1. Leone G, Mele L, Pulsoni A, Equitani F, Pagano L . The incidence of secondary leukemias. Haematologica 1999; 84: 937–945.

    CAS  Google Scholar 

  2. Seedhouse C, Russell N . Advances in the understanding of susceptibility to treatment-related acute myeloid leukaemia. Brit J Haematol 2007; 137: 513–529.

    Article  CAS  Google Scholar 

  3. Ellis NA, Huo D, Yildiz O, Worrillow LJ, Banerjee M, Le Beau MM et al. MDM2 SNP309 and TP53 Arg72Pro interact to alter therapy-related acute myeloid leukemia susceptibility. Blood 2008; 112: 741–749.

    Article  CAS  Google Scholar 

  4. Allan JM, Wild CP, Rollinson S, Willett EV, Moorman AV, Dovey GJ et al. Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapy-induced leukemia. Proc Natl Acad Sci USA 2001; 98: 11592–11597.

    Article  CAS  Google Scholar 

  5. Campone M, Roché H, Kerbrat P, Bonneterre J, Romestaing P, Fargeot P et al. Secondary leukaemia after epirubicin-based adjuvant chemotherapy in operable breast cancer patients: 16 years experience of the French Adjuvant Study Group. Ann Oncol 2005; 16: 1343–1351.

    Article  CAS  Google Scholar 

  6. Mistry AR, Felix CA, Whitmarsh RJ, Mason A, Reiter A, Cassinat B et al. DNA topoisomerase II in therapy-related acute promyelocytic leukemia. New Engl J Med 2005; 352: 1529–1538.

    Article  CAS  Google Scholar 

  7. Bolufer P, Barragan E, Collado M, Cervera J, López JA, Sanz MA . Influence of genetic polymorphisms on the risk of developing leukemia and on disease progression. Leuk Res 2006; 30: 1471–1491.

    Article  CAS  Google Scholar 

  8. Panagopoulous I, Isaksson M, Lindvall C, Björkholm M, Ahlgren T, Fioretos T et al. RT-PCR analysis of the MOZ-CPB and CBP-MOZ chimeric transcripts in acute myeloid leukemias with t(8;16)(p11;p13). Gene Chromosome Canc 2000; 28: 415–424.

    Article  Google Scholar 

  9. Seedhouse C, Faulkner R, Ashraf N, Das-Gupta E, Russell N . Polymorphisms in genes involved in homologous recombination repair interact to increase risk of developing acute myeloid leukaemia. Clin Cancer Res 2004; 10: 2675–2680.

    Article  CAS  Google Scholar 

  10. Allan JM, Smith AG, Wheatley K, Hills RK, Travis LB, Hill DA et al. Genetic variation in XPD predicts treatment outcome and risk of acute myeloid leukemia following chemotherapy. Blood 2004; 104: 3872–3877.

    Article  CAS  Google Scholar 

  11. Cascorbi I, Brockmöller J, Roots I . A C4887A polymorphism in exon 7 of human CYP1A1: population frequency, mutation linkages, and impact on lung cancer susceptibility. Cancer Res 1996; 56: 4965–4969.

    CAS  PubMed  Google Scholar 

  12. Harth V, Donat S, Ko Y, Abel J, Vetter H, Brüning T . NAD(P)H quinone oxidoreductase 1 codon 609 polymorphism and its association to colorectal cancer. Arch Toxicol 2000; 73: 528–531.

    Article  CAS  Google Scholar 

  13. Voso MT, D’Alo’ F, Putzulu R, Mele L, Scardocci A, Chiusolo P et al. Negative prognostic value of glutathione S-transferase (GSTM1 and GSTT1) deletions in adult acute myeloid leukemia. Blood 2002; 100: 2703–2707.

    Article  CAS  Google Scholar 

  14. Wilson MH, Grant PJ, Hardie LJ, Wild CP . Glutathione S-transferase M1 null genotype is associated with a decreased risk of myocardial infarction. FASEB J 2000; 14: 791–796.

    Article  CAS  Google Scholar 

  15. Levy-Lahad E, Lahad A, Eisenberg S, Dagan E, Paperna T, Kasinetz L et al. A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers. Proc Natl Acad Sci USA 2001; 98: 3232–3236.

    Article  CAS  Google Scholar 

  16. Seedhouse C, Bainton R, Lewis M, Harding A, Russell N, Das-Gupta E . The genotype distribution of the XRCC1 gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia. Blood 2002; 100: 3761–3766.

    Article  CAS  Google Scholar 

  17. Worrillow LJ, Travis LB, Smith AG, Rollinson S, Smith AJ, Wild CP et al. An intron splice acceptor polymorphism in hMSH2 and risk of leukemia after treatment with chemotherapeutic alkylating agents. Clin Cancer Res 2003; 9: 3012–3020.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology, Haemato-Oncology Diagnostic Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

    E M Boyd, A J Bench, K J Vaghela, F B Chowdhury, E J Gudgin, M A Scott & W N Erber

  2. Colchester Hospital University NHS Foundation Trust, Colchester, Essex, UK

    G N Campbell

Authors
  1. E M Boyd
    View author publications

    Search author on:PubMed Google Scholar

  2. A J Bench
    View author publications

    Search author on:PubMed Google Scholar

  3. K J Vaghela
    View author publications

    Search author on:PubMed Google Scholar

  4. G N Campbell
    View author publications

    Search author on:PubMed Google Scholar

  5. F B Chowdhury
    View author publications

    Search author on:PubMed Google Scholar

  6. E J Gudgin
    View author publications

    Search author on:PubMed Google Scholar

  7. M A Scott
    View author publications

    Search author on:PubMed Google Scholar

  8. W N Erber
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to W N Erber.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boyd, E., Bench, A., Vaghela, K. et al. Therapy-related acute myeloid leukaemia with t(8;16)(p11;p13);MOZ-CBP and polymorphisms in detoxifying and DNA repair genes. Leukemia 23, 1164–1167 (2009). https://doi.org/10.1038/leu.2008.383

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/leu.2008.383

Search

Advanced search

Quick links