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Molecular characterisation and clinical outcome of B-cell precursor acute lymphoblastic leukaemia with IG-MYC rearrangement

Lookup NU author(s): Dr Simon BomkenORCiD, Dr Amir EnshaeiORCiD, Dr Ed Schwalbe, Dr Aneta Mikulasova, Dr Masood Zaka, Kent Fung, Dr Matthew Bashton, Dr Lisa Jones, Nefeli Karataraki, Emily Winterman, Professor Vikki Rand, Dr Christopher Bacon, Dr Frederik van DelftORCiD, Professor Anthony MoormanORCiD, Dr Lisa Russell

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Abstract

Rarely, immunophenotypically immature B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) carries an immunoglobulin-MYC rearrangement (IG-MYC-r). This can result in diagnostic confusion with Burkitt lymphoma/leukaemia and use of unproven individualised treatment schedules. Here we contrast the molecular characteristics of these conditions and investigate historic clinical outcome data.We identified 90 cases registered on a national BCP-ALL clinical trial/registry. Where present, diagnostic material underwent cytogenetic, exome, methylome and transcriptome analysis. Outcome was analysed to define 3-year event free survival (EFS) and overall survival (OS).IG-MYC-r was identified in diverse cytogenetic backgrounds, co-existing with either: established BCP-ALL specific abnormalities (high hyperdiploidy n=3, KMT2A-rearrangement n=6, iAMP21 n=1, BCR-ABL n=1); BCL2/BCL6-rearrangements (n=15); or, most commonly, as the only defining feature (n=64). Within this final group, precursor-like V(D)J breakpoints predominated (8/9) and KRAS mutations were common (5/11). DNA methylation identified a cluster of V(D)J rearranged cases, clearly distinct from Burkitt leukaemia/lymphoma. Children with IG-MYC-r within that subgroup had 3-year EFS of 47% and OS of 60%, representing a high-risk BCP-ALL. To develop effective management strategies this patient group must be allowed access to contemporary, minimal residual disease adapted, prospective clinical trial protocols.


Publication metadata

Author(s): Bomken S, Enshaei A, Schwalbe EC, Mikulasova A, Dai Y, Zaka M, Fung K, Bashton M, Lim H, Jones L, Karataraki N, Winterman E, Ashby C, Attarbaschi A, Bertrand Y, Bradtke J, Buldini B, Burke GA, Cazzaniga G, Gohring G, de Groot-Kruseman H, Haferlach C, Lo Nigro L, Parihar M, Plesa A, Seaford E, Sonneveld E, Strehl S, van der Velden V, Rand V, Hunger SP, Harrison CJ, Bacon C, van Delft F, Loh M, Moppett J, Vormoor J, Walker B, Moorman AV, Russell L

Publication type: Article

Publication status: Published

Journal: Haematologica

Year: 2022

Pages: epub ahead of pub

Online publication date: 28/04/2022

Acceptance date: 31/03/2022

Date deposited: 25/07/2022

ISSN (print): 0390-6078

ISSN (electronic): 1592-8721

Publisher: Ferrata Storti Foundation

URL: https://doi.org/10.3324/haematol.2021.280557

DOI: 10.3324/haematol.2021.280557


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