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Long-term follow-up of ETV6–RUNX1 ALL reveals that NCI risk, rather than secondary genetic abnormalities, is the key risk factor

Leukemia volume 27, pages 2256–2259 (2013)Cite this article

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The ETV6–RUNX1 fusion gene is present in 25% of children diagnosed with B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) and is associated with an excellent outcome.1 Although ETV6–RUNX1-positive patients have a low relapse rate and good outcome after relapse,2 averting relapse in this prevalent subgroup warrants investigation. Previous studies investigating risk factors in this subgroup have produced inconsistent results and have been hampered by small patient cohorts and/or treatment heterogeneity.3, 4, 5, 6 ETV6–RUNX1 alone is insufficient to cause overt leukaemia and numerous cooperating mutations have been described.7 Therefore, we sought to assess the prognostic relevance of secondary abnormalities targeting the ETV6 and RUNX1 genes as well as other abnormalities (for example, IKZF1 deletion) in a large cohort of patients.

A total of 368 children with ETV6–RUNX1 BCP-ALL were treated on MRC ALL97/99.8 Both phases, ALL97 and ALL99, included a steroid and thiopurine randomization in induction and maintenance. In ALL97, patients received a 3-drug induction, 2/3 intensification blocks, central nervous system-directed treatment and continuing therapy for a total of 2 years. High-risk patients, identified by the Oxford Hazard Score or cytogenetics, were transferred to a more intensive protocol. In ALL99, children were stratified according to National Cancer Institute (NCI) risk to regimen A (standard risk (SR); <10 years and white cell count (WCC) <50 × 109 /L) or regimen B (high risk (HR); others). Patients received a 3/4-drug induction (regimen A/B) and were deemed to be slow early responders (SERs) if the day 15/8 marrow contained ⩾25% blasts. Patients who were SERs or had high-risk cytogenetics were transferred to regimen C. After induction, patients received consolidation, two interim maintenance blocks, two delayed intensification blocks and continuing therapy for a total of 2 (girls) or 3 (boys) years.

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Acknowledgements

We thank (1) Leukaemia and Lymphoma Research (formerly Leukaemia Research, UK) for financial support; (2) member laboratories of the UK Cancer Cytogenetic Group for providing cytogenetic data and material; (3) past and present members of the Leukaemia Research Cytogenetics Group for their contribution in establishing this data set; in particular, Halima Al-Shehhi, Kerry E Barber, Lucy Chilton, Amy Erhorn, Lisa Jones, Heather Morrison and Sarah Wright. Primary childhood leukaemia samples used in this study were provided by the Leukaemia and Lymphoma Research Childhood Leukaemia Cell Bank working with the laboratory teams in the Bristol Genetics Laboratory, Southmead Hospital, Bristol; Molecular Biology Laboratory, Royal Hospital for Sick Children, Glasgow; Molecular Haematology Laboratory, Royal London Hospital, London; and Molecular Genetics Service and Sheffield Children’s Hospital, Sheffield.

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Author notes

  1. A Enshaei, C J Schwab and Z J Konn: These authors contributed equally to this work.

  2. Z J Konn: Former group member.

Authors and Affiliations

  1. Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK

    A Enshaei, C J Schwab, Z J Konn, C J Harrison & A V Moorman

  2. Department of Paediatric Oncology, John Radcliffe Hospital, Oxford, UK

    C D Mitchell

  3. Department of Paediatric Haematology and Oncology, Leeds General Infirmary, Leeds, UK

    S E Kinsey

  4. Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK

    S E Kinsey

  5. Clinical Trial Service Unit, University of Oxford, Oxford, UK

    R Wade

  6. Department of Haematology, Sheffield Children’s Hospital, Sheffield, UK

    A Vora

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  1. A Enshaei
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Correspondence to A V Moorman.

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Enshaei, A., Schwab, C., Konn, Z. et al. Long-term follow-up of ETV6–RUNX1 ALL reveals that NCI risk, rather than secondary genetic abnormalities, is the key risk factor. Leukemia 27, 2256–2259 (2013). https://doi.org/10.1038/leu.2013.136

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