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Childhood ALL

Derivative chromosome 9 deletions are a significant feature of childhood Philadelphia chromosome positive acute lymphoblastic leukaemia

Leukemia volume 19, pages 564–571 (2005)Cite this article

Abstract

Deletions from the derivative chromosome 9, der(9), of the translocation, t(9;22)(q34;q11), at the site of the ABL/BCR fusion gene, have been demonstrated by fluorescence in situ hybridisation (FISH), in both Philadelphia chromosome (Ph)-positive chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL). In CML they occur in 10–15% of cases and appear to indicate a worse prognosis, whereas in ALL, the situation is unclear. This study presents the findings of dual fusion FISH used to detect such deletions in a series of 27 BCR/ABL-positive childhood ALL patients. Metaphase FISH was essential for the accurate interpretation of interphase FISH signal patterns. Three cases (11%) had a single fusion signal, resulting from deletions of the der(9). Three other patients with variant translocations and one with an insertion, also had a single fusion, but with no evidence of deletions. Gain of a fusion in approximately one-third of patients indicated a second Ph, which appears to be a diagnostic marker of Ph-positive ALL. This study shows that the incidence of deletions from the der(9) in childhood ALL is at least as high as that reported for CML.

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Acknowledgements

The authors would like to thank the Leukaemia Research Fund for financial support; Dr Mariano Rocchi, Italy, for PAC probes dJ1132H12 and dJ835J22; Dr John Crolla and his team, Wessex Regional Genetics Laboratory, Salisbury, for growing and preparation of the PAC probes; the Clinical Trial Service Unit (CTSU), Oxford, for clinical and survival data. The authors are also grateful to the following cytogenetics laboratories for providing cytogenetic and FISH data as well as fixed cell suspensions on this patient series: Academic Haematology and Cytogenetics, Royal Marsden NHS Trust, Surry; West Midlands Regional Genetics Services, Birmingham Women's Hospital; Leukaemia Cytogenetics, Addenbrooke's Hospital, Cambridge; National Centre for Medical Genetics, Our Lady's Hospital for Sick Children, Dublin; Duncan Guthrie Institute of Medical Genetics, Yorkhill NHS Trust Hospitals, Glasgow; Haematology Cytogenetic Laboratory, S.E Scotland Cytogenetic Services, Western General Hospital, Edinburgh; LRF Centre for Childhood Leukemia, Great Ormond Street Hospital, London; Oxford Medical Genetics Laboratories, Churchill Hospital, Oxford; Oncology Cytogenetics Service, Christie Hospital NHS Trust, Manchester; North Trent Cytogenetics Service, Sheffield Children's Hospital NHS Trust, Sheffield; Haematology Department, University College Hospital, London. This study could not have been performed without the dedication of the NCRI Childhood and Adult Leukaemia Working Parties and their members, who have designed and coordinated the clinical trials through which these patients were identified and through which they were treated.

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Authors and Affiliations

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

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

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  1. H M Robinson
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  2. M Martineau
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  3. R L Harris
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Correspondence to C J Harrison.

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Robinson, H., Martineau, M., Harris, R. et al. Derivative chromosome 9 deletions are a significant feature of childhood Philadelphia chromosome positive acute lymphoblastic leukaemia. Leukemia 19, 564–571 (2005). https://doi.org/10.1038/sj.leu.2403629

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