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Distribution of genomic breakpoints in chronic myeloid leukemia: analysis of 308 patients

Leukemia volume 27, pages 2105–2107 (2013)Cite this article

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Translocation breakpoints of several types of leukemia have been sequenced in order to identify factors that lead to DNA breakage (for example, topoisomerase 2 in MLL and PML-RARA leukemia).1, 2 Several studies in chronic myeloid leukemia (CML) have shown a possible association of breakpoints with ALU interspersed repeat elements (IREs),3, 4, 5, 6 but remained inconclusive due to their small sample size. We sequenced 308 BCR–ABL1 fusion genes and performed a bioinformatic analysis with greater statistical power to identify breakpoint motifs.

The research was approved by the ethics committees of the participating institutions. All CML patients in this study expressed BCR–ABL1 mRNA with breakpoints in the major breakpoint cluster region of BCR. The BCR–ABL1 genomic breakpoint was identified using one of three methods: long range,7 short range8 or inverse PCR.9 These methods rely on the fact that BCR breakpoints are tightly clustered, so that using a limited number of BCR primers it should be possible to amplify across the BCR–ABL1 junction. The success rates of the three methods were around 90%, 99% and 65%, respectively. The use of several methods with a high overall success rate avoids skewing of the data due to the limitations of a specific technique (for example, restriction enzyme sites). The data of 32 patients and five common CML cell lines were previously published.7, 10

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Acknowledgements

DMR was supported by a Leukaemia Foundation of Australia Scholarship. This study was supported in part by research funding from Novartis to DMR and TPH. Additional samples were provided by the Australasian Leukaemia and Lymphoma Group Tissue Bank.

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Authors and Affiliations

  1. Department of Haematology, Centre for Cancer Biology, SA Pathology and University of Adelaide, Adelaide, South Australia, Australia

    D M Ross, P Dang, J M Goyne, J V Melo & T P Hughes

  2. Department of Haematology and Genetic Pathology, Flinders University and Medical Centre, Adelaide, South Australia, Australia

    D M Ross, P A Bartley & A A Morley

  3. Department of Bioinformatics, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia,

    M O'Hely & T P Speed

  4. Faculty of Medicine, Wessex Regional Genetics Laboratory, Salisbury District Hospital, University of Southampton, Salisbury, UK

    J Score & N C P Cross

  5. Department of Clinical Hematology, Hospital S João, Medical Faculty of the University of Porto, Porto, Portugal

    M Sobrinho-Simoes

  6. Department of Haematology, Imperial College, London, UK

    M Sobrinho-Simoes & J V Melo

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  1. D M Ross
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  2. M O'Hely
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  9. J V Melo
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  10. T P Speed
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  11. T P Hughes
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Correspondence to D M Ross.

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Ross, D., O'Hely, M., Bartley, P. et al. Distribution of genomic breakpoints in chronic myeloid leukemia: analysis of 308 patients. Leukemia 27, 2105–2107 (2013). https://doi.org/10.1038/leu.2013.116

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