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Lookup NU author(s): Claire Schwab, Daniel Murdy, Ellie Butler, Dr Amir EnshaeiORCiD, Emily Winterman, Dr Ruth Cranston, Dr Sarra Ryan, Emilio Barretta, Zoe Hawking, James Murray, Dr Grace Antony, Professor Anthony MoormanORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd. While next-generation sequencing technologies provide excellent strategies to screen for newly defined genetic abnormalities of prognostic or therapeutic significance in patients with B-other-acute lymphoblastic leukaemia (ALL), they are not widely available. We used a dual screening approach, incorporating fluorescence in situ hybridisation (FISH) and Multiplex Ligation-dependent Probe Amplification (MLPA), to establish the frequency and long-term outcome of a representative cohort of specific subgroups of B-other-ALL recruited to the childhood ALL trial, UKALL2003. We focussed on abnormalities of known prognostic significance, including ABL-class fusions and ERG deletions, as a surrogate marker for DUX4-rearranged ALL. ABL-class fusions accounted for ~4% of B-other-ALL and were associated with high levels of minimal residual disease (MRD; 14/23 with MRD >5%) and a high relapse rate (55·7%) following treatment without tyrosine kinase inhibitor (TKI), confirming the importance of prospective screening with a view to incorporating TKI into therapy. Patients with deletions of ERG (~10% of B-other-ALL) had a 10-year event-free-survival of 97·2%, validating previous reports of their excellent outcome. Rearrangements of ZNF384, MEF2D and NUTM1 were observed at low frequencies. Here, we estimate that approximately one third of B-other-ALL patients can be reliably classified into one of the known genetic subgroups using our dual screening method. This approach is rapid, accurate and readily incorporated into routine testing.
Author(s): Schwab CJ, Murdy D, Butler E, Enshaei A, Winterman E, Cranston RE, Ryan S, Barretta E, Hawking Z, Murray J, Antony G, Vora A, Moorman AV, Harrison CJ
Publication type: Article
Publication status: Published
Journal: British Journal of Haematology
Year: 2022
Volume: 196
Issue: 3
Pages: 753-763
Print publication date: 01/02/2022
Online publication date: 21/10/2021
Acceptance date: 09/09/2021
Date deposited: 03/11/2021
ISSN (print): 0007-1048
ISSN (electronic): 1365-2141
Publisher: John Wiley and Sons Inc.
URL: https://doi.org/10.1111/bjh.17869
DOI: 10.1111/bjh.17869
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