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Acute Lymphoblastic Leukemia

Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases

Abstract

This study identifies multiple copies of the AML1 gene on a duplicated chromosome 21, dup(21), as a recurrent abnormality in acute lymphoblastic leukemia (ALL). Clusters of AML1 signals were visible at interphase by fluorescence in situ hybridization (FISH). In metaphase, they appeared tandemly duplicated on marker chromosomes of five distinct morphological types: large or small acrocentrics, metacentrics, submetacentrics or rings. The markers comprised only chromosome 21 material. Karyotypes were near-diploid and, besides dup(21), no other established chromosomal changes were observed. A total of 20 patients, 1.5 and <0.5% among consecutive series of childhood and adult ALL respectively, showed this phenomenon. Their median age was 9 years, white cell counts were low and all had a pre-B/common immunophenotype. Although this series is not the first report of this abnormality, it is the largest, permitting a detailed description of the variety of morphological forms that duplicated chromosome 21 can assume.

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Acknowledgements

We thank the Leukaemia Research Fund for financial support and the UK cytogenetics laboratories that contributed samples to this study: Belfast, Birmingham, Cambridge, Cardiff, Croydon, Dundee, Edinburgh, Great Ormond Street Children's Hospital, London, Manchester, Newcastle, Norwich, Royal Marsden Hospital, London, Salisbury, Sheffield, and University College Hospital, London. Cosmids ICRF c103 CO664 and H11086 were kindly donated by Dr Anne Hagermeijer, EU Concerted Action and Dr Roland Berger, Paris, respectively. We are grateful to Dr John Crolla and his team, Wessex Regional Genetics Laboratory, Salisbury for the growing and preparation of the AML1 specific cosmids as part of an ongoing collaboration. We thank Dr Helena Kempski for helpful discussions.

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Harewood, L., Robinson, H., Harris, R. et al. Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases. Leukemia 17, 547–553 (2003). https://doi.org/10.1038/sj.leu.2402849

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Keywords

  • amplified AML1
  • acute lymphoblastic leukemia
  • duplicated chromosome 21

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