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.

  • Original Article
  • Published:

Acute Non-Lymphocytic Leukemias

Population-based demographic study of karyotypes in 1709 patients with adult Acute Myeloid Leukemia

Leukemia volume 20, pages 444–450 (2006)Cite this article

Abstract

Few large demographic studies of acute myeloid leukemia (AML) are derived from population-based registries. Demographic and karyotypic data were provided for AML cases from two regional leukemia registry databases in Scotland and the Northern Region of England. A population-based dataset was compiled, comprising 1709 patients aged >16 years (1235 North England/474 Scotland patients). The most common cytogenetic abnormalities involved chromosomes 5 and/or 7 (17%). Patients with the following abnormal chromosome 5/7 combinations: −5, del(5q), −5/−7 and del(5q)/−7 represented a significantly older population (P<0.01, ANOVA). t(8;21) was the only ‘favourable’ karyotype found in older age. Karyotypic complexity varied within chromosome 5/7 combination groups; those containing −5, −5/−7, −5/del(7q), del(5q)/−7 or del(5q)/del(7q) combinations were significantly more frequently complex than those containing −7 and del(7q) (P<0.01, χ2 test). Additional recurring cytogenetic abnormalities within complex karyotypes containing chromosome 5/7 combinations included (in order of frequency), abnormalities of chromosomes 17, 12, 3 and 18. Complex karyotypes not involving chromosomes 5 or 7 represented 30% of all complex karyotypes, occurred in younger patients than those involving chromosomes 5 and 7, and frequently included additional trisomy 8 (26%). In conclusion, we describe subgroups within adverse karyotypes, with different demographics, degree of complexity and additional chromosome abnormalities.

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

Similar content being viewed by others

References

  1. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 1976; 33: 451–458.

    Article  CAS  Google Scholar 

  2. Bennett JM . World Health Organization classification of the acute leukemias and myelodysplastic syndrome. Int J Hematol 2000; 72: 131–133.

    CAS  PubMed  Google Scholar 

  3. Rowley JD, Golomb HM . The 4th International Workshop on chromosomes in leukemia – a prospective study of acute non-lymphocytic leukemia, Chicago, Illinois, USA, September 2–7 1982. Cancer Genetics And Cytogenetics 1984; 11: 249.

    Google Scholar 

  4. Bloomfield CD, Shuma C, Regal L, Philip PP, Hossfeld DK, Hagemeijer AM et al. Long-term survival of patients with acute myeloid leukemia: a third follow-up of the Fourth International Workshop on Chromosomes in Leukemia. Cancer 1997; 80 (11 Suppl): 2191–2198.

    Article  CAS  Google Scholar 

  5. 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 1,612 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 

  6. Wheatley K, Burnett AK, Goldstone AH, Gray RG, Hann IM, Harrison CJ et al. A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial. United Kingdom Medical Research Council's Adult and Childhood Leukaemia Working Parties. Br J Haematol 1999; 107: 69–79.

    Article  CAS  Google Scholar 

  7. Taylor PR, Reid MM, Stark AN, Bown N, Hamilton PJ, Proctor SJ . De novo acute myeloid leukaemia in patients over 55-years-old: a population-based study of incidence, treatment and outcome. Northern Region Haematology Group. Leukemia 1995; 9: 231–237.

    Google Scholar 

  8. Proctor SJ, Taylor PR . Age cohort subgroups in adult acute myeloid leukaemia studies – the population perspective. Leukemia 2001; 15: 188–189.

    Article  CAS  Google Scholar 

  9. Preiss BS, Kerndrup GB, Schmidt KG, Sorensen AG, Clausen NA, Gadeberg OV et al. Cytogenetic findings in adult de novo acute myeloid leukaemia. A population-based study of 303/337 patients. Br J Haematol 2003; 123: 219–234.

    Article  Google Scholar 

  10. Mitelman F . ISCN: An international system for human cytogenetic nomenclature. Basel, Switzerland: Karger, 1995.

    Google Scholar 

  11. Moorman AV, Roman E, Willett EV, Dovey GJ, Cartwright RA, Morgan GJ et al. Karyotype and age in acute myeloid leukemia Are they linked? Cancer Genet Cytogenet 2001; 126: 155–161.

    Article  CAS  Google Scholar 

  12. Schoch C, Kern W, Krawitz P, Dugas M, Schnittger S, Haferlach T et al. Dependence of age-specific incidence of acute myeloid leukemia on karyotype. Blood 2001; 98: 3500.

    Article  CAS  Google Scholar 

  13. Mauritzson N, Johansson B, Albin M, Billstrom R, Ahlgren T, Mikoczy Z et al. A single-center population-based consecutive series of 1500 cytogenetically investigated adult hematological malignancies: karyotypic features in relation to morphology, age and gender. Eur J Haematol 1999; 62: 95–102.

    Article  CAS  Google Scholar 

  14. Moorman AV, Roman E, Cartwright RA, Morgan GJ . Patients entered into MRC AML trials are biologically representative of the totality of the disease in the UK. Clin Lab Haematol 2002; 24: 263–265.

    Article  CAS  Google Scholar 

  15. Moorman AV, Roman E, Cartwright RA, Morgan GJ . Age-specific incidence rates for cytogenetically-defined subtypes of acute myeloid leukaemia. Br J Cancer 2002; 86: 1061–1063.

    Article  CAS  Google Scholar 

  16. Vickers M, Jackson G, Taylor P . The incidence of acute promyelocytic leukemia appears constant over most of a human lifespan, implying only one rate limiting mutation. Leukemia 2000; 14: 722–726.

    Article  CAS  Google Scholar 

  17. Mertens F, Johansson B, Mitelman F . Age- and gender-related heterogeneity of cancer chromosome aberrations. Cancer Genet Cytogenet 1993; 70: 6–11.

    Article  CAS  Google Scholar 

  18. Cartwright RA, Gurney KA, Moorman AV . Sex ratios and the risks of haematological malignancies. Br J Haematol 2002; 118: 1071–1077.

    Article  Google Scholar 

  19. Grimwade D, Walker H, Harrison G, Oliver F, Chatters S, Harrison CJ et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 2001; 98: 1312–1320.

    Article  CAS  Google Scholar 

  20. Schoch C, Haferlach T, Bursch S, Gerstner D, Schnittger S, Dugas M et al. Loss of genetic material is more common than gain in acute myeloid leukemia with complex aberrant karyotype: a detailed analysis of 125 cases using conventional chromosome analysis and fluorescence in situ hybridization including 24-color FISH. Genes Chromosomes Cancer 2002; 35: 20–29.

    Article  Google Scholar 

  21. Pedersen-Bjergaard J, Andersen MK, Christiansen DH, Nerlov C . Genetic pathways in therapy-related myelodysplasia and acute myeloid leukemia. Blood 2002; 99: 1909–1912.

    Article  CAS  Google Scholar 

  22. Castro PD, Liang JC, Nagarajan L . Deletions of chromosome 5q133 and 17p loci cooperate in myeloid neoplasms. Blood 2000; 95: 2138–2143.

    CAS  PubMed  Google Scholar 

  23. Van Limbergen H, Poppe B, Michaux L, Herens C, Brown J, Noens L et al. Identification of cytogenetic subclasses and recurring chromosomal aberrations in AML and MDS with complex karyotypes using M-FISH. Genes Chromosomes Cancer 2002; 33: 60–72.

    Article  CAS  Google Scholar 

  24. Crescenzi B, Lastarza R, Romoli S, Beacci D, Matteucci C, Barba G et al. Submicroscopic deletions in 5q- associated malignancies. Haematologica 2004; 89: 281–285.

    CAS  PubMed  Google Scholar 

  25. Paulsson K, Sall T, Fioretos T, Mitelman F, Johansson B . The incidence of trisomy 8 as a sole chromosomal aberration in myeloid malignancies varies in relation to gender, age, prior iatrogenic genotoxic exposure, and morphology. Cancer Genet Cytogenet 2001; 130: 160–165.

    Article  CAS  Google Scholar 

  26. Wolman SR, Gundacker H, Appelbaum FR, Slovak ML . Impact of trisomy 8 (+8) on clinical presentation, treatment response, and survival in acute myeloid leukemia: a Southwest Oncology Group study. Blood 2002; 100: 29–35.

    Article  CAS  Google Scholar 

  27. Schoch C, Haase D, Fonatsch C, Haferlach T, Loffler H, Schlegelberger B et al. The significance of trisomy 8 in de novo acute myeloid leukaemia: the accompanying chromosome aberrations determine the prognosis. German AML Cooperative Study Group. Br J Haematol 1997; 99: 605–611.

    Article  CAS  Google Scholar 

  28. Nilsson L, Astrand-Grundstrom I, Anderson K, Arvidsson I, Hokland P, Bryder D et al. Involvement and functional impairment of the CD34+CD38-Thy−1+ hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8. Blood 2002; 100: 259–267.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The Hematology Units in Scotland, and the North East of England, who contributed invaluable data to the respective registries. The assistance of Christine Maguire and Jo White in the Scotland Leukaemia Registry is gratefully acknowledged. We are grateful to Dr. David Grimwade for critical review of the manuscript. PRT is supported by the Newcastle upon Tyne Hospitals Regional Research and Development Fund. The Scotland Leukaemia Registry was generously supported by a grant from the Lloyds/TSB Research Foundation.

Author information

Author notes

  1. A V Moorman: Leukaemia Department of Hematology, Leeds Technology Hospital, Leeds LS13EX, UK

  2. E Roman and E Willett: Epidemiology and Genetics Unit, University of York, York, UK

  3. D T Bowen: Department of Haematology, Leeds Teaching Hospitals, UK

Authors and Affiliations

  1. Division of Pathology & Neuroscience, University of Dundee, Dundee, UK

    R N Sanderson & D T Bowen

  2. Department of Hematology, Western General Hospital, Edinburgh, UK

    P R E Johnson

  3. Leukaemia Research Fund Epidemiology Unit, University of Leeds, Leeds, UK

    A V Moorman, E Roman & E Willett

  4. Department of Hematology, Royal Victoria Infirmary, Newcastle, UK

    P R Taylor & S J Proctor

  5. Northern Genetics Service, Centre for Life, Newcastle, UK

    N Bown

  6. Division of Community Health Sciences, University of Dundee, Dundee, UK

    S Ogston

Authors
  1. R N Sanderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P R E Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A V Moorman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Roman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E Willett
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P R Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S J Proctor
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. N Bown
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S Ogston
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. D T Bowen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D T Bowen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sanderson, R., Johnson, P., Moorman, A. et al. Population-based demographic study of karyotypes in 1709 patients with adult Acute Myeloid Leukemia. Leukemia 20, 444–450 (2006). https://doi.org/10.1038/sj.leu.2404055

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404055

Keywords

This article is cited by

Search

Advanced search

Quick links