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Lookup NU author(s): Claire Schwab,
Dr Amir EnshaeiORCiD,
Dr Ruth Cranston,
Dr Sarra Ryan,
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
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.
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