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Cytogenetics and Molecular Genetics

Hyperdiploidy with 49–65 chromosomes represents a heterogeneous cytogenetic subgroup of acute myeloid leukemia with differential outcome

Leukemia volume 28, pages 321–328 (2014)Cite this article

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Abstract

Chromosome gain is frequent in acute myeloid leukemia (AML) and is counted alongside structural abnormalities when determining karyotype complexity. However, there are few studies investigating the cytogenetic profile and outcome of patients with a hyperdiploid karyotype (49–65 chromosomes, HK). We identified 221 (14%) patients with HK out of 1563 patients with three or more chromosomal abnormalities. HK was not associated with sex, white cell count and secondary disease status, but was more prevalent among children (22% vs 13%). The pattern of chromosomal gain and loss was non-random and chromosomes 8, 13 and 21 were the most frequently gained. Three distinct subgroups (numerical, structural and adverse) were identified with differential outcome: 5-year cumulative incidence of relapse of 52%, 68% and 76%, respectively (P=0.008). Patients in the adverse subgroup had poorer survival compared with patients with only numerical abnormalities (adjusted hazard ratio: 2.01 (95% confidence interval: 1.43–2.83), P=0.0002). This outcome heterogeneity was similar among children and adults. In conclusion, AML patients with a HK should not automatically be assigned to the adverse cytogenetic risk group on the basis of complexity. Instead they should be assessed for the presence of specific chromosomal abnormalities, which are known to harbour an adverse effect.

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Acknowledgements

We thank all the clinicians participating in the MRC/National Cancer Research Institute trials and members of laboratories of the United Kingdom Cancer Cytogenetics Group (UKCCG) and cytogenetic laboratories from Denmark and New Zealand. DG, CJH and AVM are grateful to Leukaemia and Lymphoma Research, UK, for funding; DG, RKH and AKB also acknowledge support from the National Institute for Health Research and the European LeukemiaNet. The MRC trials databases have been supported by Kay Kendall Leukaemia Fund and Leukaemia and Lymphoma Research.

Author contributions

LC, RKH, DG and AVM designed the study and wrote the manuscript; RKH and LC performed statistical analyses; AVM and CJH classified the cytogenetic abnormalities and managed the cytogenetics database; AKB was the lead participant in the MRC AML trials; and all authors approved the final version of the manuscript.

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Author notes

  1. L Chilton and R K Hills: These authors contributed equally to this work.

Authors and Affiliations

  1. Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Level 5, Sir James Spence Institute, Newcastle University, Newcastle upon Tyne, UK

    L Chilton, C J Harrison & A V Moorman

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

    R K Hills & A K Burnett

  3. Department of Medical and Molecular Genetics, King’s College London School of Medicine, London, UK

    D Grimwade

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  1. L Chilton
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  2. R K Hills
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Correspondence to A V Moorman.

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Chilton, L., Hills, R., Harrison, C. et al. Hyperdiploidy with 49–65 chromosomes represents a heterogeneous cytogenetic subgroup of acute myeloid leukemia with differential outcome. Leukemia 28, 321–328 (2014). https://doi.org/10.1038/leu.2013.198

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