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Relapse of BCR-ABL1-like ALL mediated by the ABL1 kinase domain mutation T315I following initial response to dasatinib treatment

Leukemia volume 29, pages 230–232 (2015)Cite this article

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The addition of tyrosine kinase inhibitors (TKIs) to conventional chemotherapy regimens has improved the response rates for patients with Philadelphia-positive (BCR-ABL1-positive) acute lymphoblastic leukaemia (ALL), though outcomes remain generally inferior compared to BCR-ABL1-negative ALL cases.1 Kinase domain mutations, such as T315I, are commonly seen at disease relapse.2

Recent genomic analysis has revealed a subgroup of BCR-ABL1-negative ALL cases with similar gene expression profiles to those observed in BCR-ABL1-positive cases.3,4 Many of these BCR-ABL1-like cases have been subsequently found to harbour cryptic gene rearrangements leading to constitutively active tyrosine kinases such as ABL1, ABL2 and PDGFRB among others.5 BCR-ABL1-positive and BCR-ABL1-like ALL have equally inferior clinical outcomes when compared to other standard risk cases and comprise ~9% of paediatric ALL cases.6 The incidence of this molecular subtype is estimated to be more prevalent in older patients, as demonstrated by Roberts et al.7 in a recent report. Formal surveys of incidence and outcome in age groups other than children are currently underway.

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Acknowledgements

DTY is supported by a PhD scholarship from the Leukaemia Foundation of Australia and the Royal Adelaide Hospital Research AR Clarkson Foundation. TPH is a NHMRC Practitioner Fellow. This project was funded by a Beat Cancer Grant from the Cancer Council of SA, an Australasian Leukaemia and Lymphoma Group start-up Grant and subsequently by an NHMRC project grant.

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Authors and Affiliations

  1. Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia

    D T Yeung, D J Moulton, C G Mullighan, T P Hughes & D L White

  2. Department of Genetics & Pathology & Centre for Cancer Biology, Adelaide, South Australia, Australia,

    D T Yeung, J Braley, S Branford & S Moore

  3. Department of Haematology, SA Pathology, Adelaide, South Australia, Australia

    D T Yeung, D J Moulton & T P Hughes

  4. South Australia Health and Medical Research Institute, Adelaide, South Australia, Australia

    D J Moulton, S L Heatley, E Nievergall, P Dang, C G Mullighan, T P Hughes & D L White

  5. St Jude Children's Research Hospital, Memphis, TN, USA

    C G Mullighan

  6. Discipline of Paediatrics, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia

    D L White

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  1. D T Yeung
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Competing interests

TPH has received honoraria, participated on the advisory boards of, and received research funding from BMS, Novartis and Ariad. DLW and SB have received honoraria and research funding from BMS, Novartis and Ariad. DTY has received honoraria, participated on the advisory boards of and received research funding from BMS and Novartis. The remaining authors declare no conflict of interest.

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Yeung, D., Moulton, D., Heatley, S. et al. Relapse of BCR-ABL1-like ALL mediated by the ABL1 kinase domain mutation T315I following initial response to dasatinib treatment. Leukemia 29, 230–232 (2015). https://doi.org/10.1038/leu.2014.256

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