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Investigation on the role of the ATM gene in chronic myeloid leukaemia

Leukemia volume 15, pages 1448–1450 (2001)Cite this article

Abstract

Chronic myeloid leukaemia (CML) is characterised by an indolent, chronic phase (CP) preceding an acute transformation to blast crisis (BC). While the BCR-ABL fusion oncogene is strongly implicated in the CP, the molecular changes underlying BC are largely unknown. The ataxia telangiectasia gene, ATM, is a candidate gene for this transformation because the complex karyotypes associated with BC of CML suggest that DNA double-strand break repair is defective and because the ABL pathway involves the interaction between the Abl and the Atm proteins. We performed a mutational analysis for ATM in CML using genomic DNA from 14 CML cell lines and 59 CML patients in BC. No clearly deleterious nucleotide changes were observed. A new polymorphism C4138T was discovered which results in a non-conservative amino acid substitution (H1380Y). This variant lies in the Atm recognition motif for the Abl protein. While ATM is unlikely to contribute substantially to CML, further investigation of the H1380Y substitution should clarify whether it has any functional effect.

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Acknowledgements

We acknowledge support from the Kay Kendall Leukaemia Trust and the Leukaemia Research Fund. AGvD was a student on placement from the University of Manchester. We thank PS Bradshaw for critically reading the manuscript.

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Authors and Affiliations

  1. Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, UK

    JV Melo, A Kumberova & JM Goldman

  2. Academic Department of Haematology and Cytogenetics, UK, Institute of Cancer Research, Sutton, UK

    AG van Dijk & MR Yuille

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  1. JV Melo
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  2. A Kumberova
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  4. JM Goldman
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Melo, J., Kumberova, A., van Dijk, A. et al. Investigation on the role of the ATM gene in chronic myeloid leukaemia. Leukemia 15, 1448–1450 (2001). https://doi.org/10.1038/sj.leu.2402223

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