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Amplification of the ABL gene in T-cell acute lymphoblastic leukemia

Leukemia volume 18, pages 1153–1156 (2004)Cite this article

TO THE EDITOR

The Leukaemia Research Fund UK Cancer Cytogenetics Group Karyotype Database in Acute Leukaemia (Database)1 would like to inform readers of a new finding. We observed amplification involving the ABL gene in acute lymphoblastic leukemia (ALL), which appeared as multiple signals by fluorescence in situ hybridization (FISH) in eight patients with T-lineage ALL. Gene amplification is a frequent finding in a wide range of tumors but has been rarely described in acute leukemia. In cytogenetic preparations, it is usually seen intrachromosomally as homogeneously staining regions (HSR) or extrachromosomally as double minutes (dmin). FISH studies have revealed the genes involved in the amplified regions. Amplifications of the MYC and MLL genes have been previously reported in acute myeloid leukemia (AML),2,3,4 and of AML1 and MLL in ALL.3,5 Although amplification of the BCR/ABL fusion gene has been described in cases of chronic myeloid leukemia (CML) treated with imatinib mesylate, seen both as HSRs6 and dmins,7 amplification of ABL alone is rare. A six-fold and a 15-fold amplification of the gene have been described in the CML-derived cell line, K562,8 and in a patient with CML in lymphoid blast crisis, respectively.9 The only other FISH report of amplification involving ABL was in three cases of secondary AML.10

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References

  1. Harrison CJ, Martineau M, Secker-Walker LM . The Leukaemia Research Fund/United Kingdom Cancer Cytogenetics Group Karyotype Database in acute lymphoblastic leukaemia: a valuable resource for patient management. Br J Haematol 2001; 113: 3–10.

    Article  CAS  Google Scholar 

  2. Crossen PE, Savage LM, Heaton DC, Morrison MJ . Characterization of the C-MYC amplicon in a case of acute myeloid leukemia with double minute chromosomes. Cancer Genet Cytogenet 1999; 112: 144–148.

    Article  CAS  Google Scholar 

  3. Cuthbert G, Thompson K, McCullough S, Watmore A, Dickinson H, Telford N et al MLL amplification in acute leukaemia: a United Kingdom Cancer Cytogenetics Study Group (UKCCG) study. Leukemia 2000; 14: 1885–1891.

    Article  CAS  Google Scholar 

  4. Sait SN, Qadir MU, Conroy JM, Matsui S, Nowak NJ, Baer MR . Double minute chromosomes in acute myeloid leukemia and myelodysplastic syndrome: identification of new amplification regions by fluorescence in situ hybridization and spectral karyotyping. Genes Chromosomes Cancer 2002; 34: 42–47.

    Article  CAS  Google Scholar 

  5. Harewood L, Robinson H, Harris R, Jabbar Al-Obaidi MS, Jalali GR, Martineau M et al Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases. Leukemia 2003; 17: 547–553.

    Article  CAS  Google Scholar 

  6. Campbell LJ, Patsouris C, Rayeroux KC, Somana K, Januszewicz EH, Szer J . BCR/ABL amplification in chronic myelocytic leukemia blast crisis following imatinib mesylate administration. Cancer Genet Cytogenet 2002; 139: 30–33.

    Article  CAS  Google Scholar 

  7. Morel F, Bris MJ, Herry A, Calvez GL, Marion V, Abgrall JF et al Double minutes containing amplified bcr-abl fusion gene in a case of chronic myeloid leukemia treated by imatinib. Eur J Haematol 2003; 70: 235–239.

    Article  Google Scholar 

  8. Collins SJ, Groudine MT . Rearrangement and amplification of c-abl sequences in the human chronic myelogenous leukemia cell line K-562. Proc Natl Acad Sci USA 1983; 80: 4813–4817.

    Article  CAS  Google Scholar 

  9. Kenner L, Beham-Schmid C, Kerbl R, Schmidt HH, Sill H, Hoefler G . ABL amplification in a patient with lymphoid blast crisis of chronic myelogenous leukaemia. Virchows Arch 1999; 434: 255–257.

    Article  CAS  Google Scholar 

  10. Tanaka K, Arif M, Eguchi M, Kyo T, Dohy H, Kamada N . Frequent jumping translocations of chromosomal segments involving the ABL oncogene alone or in combination with CD3-MLL genes in secondary leukemias. Blood 1997; 89: 596–600.

    CAS  PubMed  Google Scholar 

  11. ISCN. An International System for Human Cytogenetic Nomenclature, 1st edn. Basel: S Karger, 1995.

  12. Vaillant F, Blyth K, Terry A, Bell M, Cameron ER, Neil J et al. A full-length Cbfa1 gene product perturbs T-cell development and promotes lymphomagenesis in synergy with myc. Oncogene 1999; 18: 7124–7134.

    Article  CAS  Google Scholar 

  13. Mao X, Lillington D, Child F, Russell-Jones R, Young B, Whittaker S . Comparative genomic hybridization analysis of primary cutaneous B-cell lymphomas: identification of common genomic alterations in disease pathogenesis. Genes Chromosomes Cancer 2002; 35: 144–155.

    Article  CAS  Google Scholar 

  14. Mao X, Onadim Z, Price EA, Child F, Lillington DM, Russell-Jones R et al Genomic alterations in blastic natural killer/extranodal natural killer-like T cell lymphoma with cutaneous involvement. J Invest Dermatol 2003; 121: 618–627.

    Article  CAS  Google Scholar 

  15. Mao X, Orchard G, Lillington DM, Russell-Jones R, Young BD, Whittaker S . Genetic alterations in primary cutaneous CD30+ anaplastic large cell lymphoma. Genes Chromosomes Cancer 2003; 37: 176–185.

    Article  CAS  Google Scholar 

  16. Jack EM, Harrison CJ, Allen TD, Harris R . A scanning electron microscope study of double minutes from a human tumour cell line. Cytogenet Cell Genet 1987; 44: 49–52.

    Article  CAS  Google Scholar 

  17. Von Hoff DD, Needham-VanDevanter DR, Yucel J, Windle BE, Wahl GM . Amplified human MYC oncogenes localized to replicating submicroscopic circular DNA molecules. Proc Natl Acad Sci USA 1988; 85: 4804–4808.

    Article  CAS  Google Scholar 

  18. Maurer BJ, Lai E, Hamkalo BA, Hood L, Attardi G . Novel submicroscopic extrachromosomal elements containing amplified genes in human cells. Nature 1987; 327: 434–437.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the Leukaemia Research Fund for financial support and the following UKCCG laboratories for providing samples for this study: Glasgow, Leeds, Leicester, Manchester, Nottingham, Cambridge, Salisbury and Oxford. We are also grateful to Dr M Rocchi (Resources in Molecular Cytogenetics, Bari, Italy) for kindly donating the ABL-specific PAC probes and to Dr John Crolla (Wessex Regional Genetics Laboratories, Salisbury) for growing and preparing these PAC probes as part of an ongoing collaborative study. This study could not have been performed without the dedication of the members of Medical Research Council Adult and Childhood Leukaemia Working Parties, who have designed and coordinated the clinical trials through which these patients were identified and on which they were treated.

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Authors and Affiliations

  1. Cancer Sciences Division, Leukaemia Research Fund Cytogenetics Group, University of Southampton, Southampton, UK

    K E Barber, M Martineau, L Harewood, Z J Broadfield, K L Cheung, R L Harris, G R Jalali, A V Moorman, H M Robinson & C J Harrison

  2. Institute of Comparative Medicine, Glasgow University Veterinary School, Glasgow, UK

    M Stewart & E Cameron

  3. The Orchid Cancer Appeal, Cancer Research UK Medical Oncology Unit, London, UK

    J C Strefford

  4. Structural Cell Biology, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK

    S Rutherford & T D Allen

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  1. K E Barber
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  2. M Martineau
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  3. L Harewood
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  8. T D Allen
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  10. K L Cheung
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  12. G R Jalali
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  14. H M Robinson
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  15. C J Harrison
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Correspondence to C J Harrison.

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Barber, K., Martineau, M., Harewood, L. et al. Amplification of the ABL gene in T-cell acute lymphoblastic leukemia. Leukemia 18, 1153–1156 (2004). https://doi.org/10.1038/sj.leu.2403357

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  • DOI: https://doi.org/10.1038/sj.leu.2403357

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