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

Simon Bomken, Amir Enshaei, Ed Schwalbe, Aneta Mikulasova, Yunfeng Dai, Masood Zaka, Kent Tm Fung, Matthew Bashton, Huezin Lim, Lisa Jones, Nefeli Karataraki, Emily Winterman, Cody Ashby, Andishe Attarbaschi, Yves Bertrand, Jutte Bradtke, Barbara Buldini, G.A. Amos Burke, Giovanni Cazzaniga, Gudrun GohringHesta A. De Groot-Kruseman, Claudia Haferlach, Luca Lo Nigro, Mayur Parihar, Adriana Plesa, Emma Seaford, Edwin Sonneveld, Sabine Strehl, Vincent H.J. Van der Velden, Vikki Rand, Stephen P. Hunger, Christine J. Harrison, Chris M. Bacon, Frederik W. Van Delft, Mignon L. Loh, John Moppett, Josef Vormoor, Brian A. Walker, Anthony Vincent Moorman, Lisa J. Russell

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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.

Original languageEnglish
JournalHaematologica
Early online date28 Apr 2022
DOIs
Publication statusE-pub ahead of print - 28 Apr 2022

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