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Acute Leukemias

An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome

Leukemia volume 28, pages 1015–1021 (2014)Cite this article

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Abstract

Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). To date, fluorescence in situ hybridisation (FISH), with probes specific for the RUNX1 gene, provides the only reliable detection method (five or more RUNX1 signals per cell). Patients with iAMP21 are older (median age 9 years) with a low white cell count. Previously, we demonstrated a high relapse risk when these patients were treated as standard risk. Recent studies have shown improved outcome on intensive therapy. In view of these treatment implications, accurate identification is essential. Here we have studied the cytogenetics and outcome of 530 iAMP21 patients that highlighted the association of specific secondary chromosomal and genetic changes with iAMP21 to assist in diagnosis, including the gain of chromosome X, loss or deletion of chromosome 7, ETV6 and RB1 deletions. These iAMP21 patients when treated as high risk showed the same improved outcome as those in trial-based studies regardless of the backbone chemotherapy regimen given. This study reinforces the importance of intensified treatment to reduce the risk of relapse in iAMP21 patients. This now well-defined patient subgroup should be recognised by World Health Organisation (WHO) as a distinct entity of BCP-ALL.

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Acknowledgements

We thank the member laboratories of the UK Cancer Cytogenetics Group, the National Cancer Research Institute and Childhood Leukaemia Subgroup, UK, those cytogenetics laboratories contributing to the COG trails in the United States and all other participating cytogenetics laboratories and treating physicians worldwide. We are grateful for financial support from Leukaemia and Lymphoma Research, Grants CA13539 and CA98543 from the National Institutes of Health to the COG, Swedish Childhood Cancer Foundation, FWO-Vlaanderen, Vlaamse liga tegen Kanker and NKP 29-020, Jubilämsfonds Österreichische Nationalbank (ÖNB No. 14133).

Author contributions

CJH, OAH and AVM designed the study. CJH and AVM organised data collection. CJH and CS analysed the cytogenetic, FISH and MLPA data. CS, AJC and NAH reviewed the cytogenetic data. CS, SS and KN carried out and interpreted the MLPA data. CS, AJC, EAR, MD, SS, KN, JH, AT-S, MZ, ND, AB, JS, M-FA, AA, GM, BS, GC, LC, PV, EF, IH, SCR, MP, J-PB, JT, CH, AV, SPH, NAH and OAH contributed cytogenetic, FISH and/or SNP data and/or clinical and follow-up data. CJH, AVM, SPH and OAH wrote the manuscript that was critically reviewed by all authors.

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Authors and Affiliations

  1. Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK

    C J Harrison, A V Moorman, C Schwab & L Chilton

  2. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

    A J Carroll

  3. The New York University Cancer Institute, New York University Langone Medical Center, New York, NY, USA

    E A Raetz

  4. University of Florida, Gainesville, FL, USA

    M Devidas

  5. Children’s Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, Austria

    S Strehl, K Nebral, A Attarbaschi, G Mann & O A Haas

  6. Department of Paediatric Haematology and Oncology, Oncogenetic Laboratory, Justus-Liebig-University, Giessen, Germany

    J Harbott & A Teigler-Schlegel

  7. Department of Pediatric Hematology/Oncology, Medical School Hannover, Hannover, Germany

    M Zimmerman

  8. Laboratoire d'hématologie, Génétique des Hémopathies, Hôpital Purpan, Toulouse, France

    N Dastuge

  9. Pediatric Hematology-Immunology, Hôpital Robert Debré (AP-HP), Paris, France

    A Baruchel & M-F Auclerc

  10. Saint-Louis hospital APHP and Hematology University Institute (IUH), University Paris-Diderot, Paris, France

    J Soulier

  11. Pediatric Hemato/Oncology Center, Schneider Children's Medical Center of Israel, Petach-Tikva, Israel

    B Stark

  12. Centro Ricerca Tettamanti, Clinica Pediatrica, University of Milano-Bicocca, Milan, Italy

    G Cazzaniga

  13. Center for Human Genetics, University of Leuven, Leuven, Belgium

    P Vandenberghe

  14. Department of Medical Biosciences, Genetics, Umeå University Hospital, Umeå, Sweden

    E Forestier

  15. Departments of Pediatrics, Semmelweis University of Medicine, Budapest, Hungary

    I Haltrich

  16. Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA

    S C Raimondi

  17. Department of Cytogenetics and Laboratory Hematology Tata Medical Center, Kolkata, West Bengal, India

    M Parihar

  18. Department of Oncology and Children's Research Center, University Hospital Zurich, Zurich, Switzerland

    J-P Bourquin & J Tchinda

  19. MLL, Munich Leukemia Laboratory, Munich, Germany

    C Haferlach

  20. Sheffield Children’s Hospital, Sheffield, UK

    A Vora

  21. Children’s Hospital Colorado, and University of Colorado School of Medicine, Aurora, CO, USA

    S P Hunger

  22. Department of Pathology, Ohio State University, Columbus, OH, USA

    N A Heerema

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  1. C J Harrison
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  32. O A Haas
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on behalf of the Ponte di Legno International Workshop in Childhood Acute Lymphoblastic Leukemia

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Correspondence to C J Harrison.

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Harrison, C., Moorman, A., Schwab, C. et al. An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome. Leukemia 28, 1015–1021 (2014). https://doi.org/10.1038/leu.2013.317

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