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.

Bomken, S., Enshaei, A., Schwalbe, E., Mikulasova, A., Dai, Y., Zaka, M., et al. (2022). Molecular characterisation and clinical outcome of B-cell precursor acute lymphoblastic leukaemia with IG-MYC rearrangement. HAEMATOLOGICA [10.3324/haematol.2021.280557].

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

Cazzaniga, Giovanni;
2022

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.
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Articolo in rivista - Articolo scientifico
Scientifica
B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) immunoglobulin-MYC rearrangement (IG-MYC-r)
English
Bomken, S., Enshaei, A., Schwalbe, E., Mikulasova, A., Dai, Y., Zaka, M., et al. (2022). Molecular characterisation and clinical outcome of B-cell precursor acute lymphoblastic leukaemia with IG-MYC rearrangement. HAEMATOLOGICA [10.3324/haematol.2021.280557].
Bomken, S; Enshaei, A; Schwalbe, E; 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, G; Cazzaniga, G; Gohring, G; De Groot-Kruseman, H; Haferlach, C; Nigro, L; Parihar, M; Plesa, A; Seaford, E; Sonneveld, E; Strehl, S; Van der Velden, V; Rand, V; Hunger, S; Harrison, C; Bacon, C; Van Delft, F; Loh, M; Moppett, J; Vormoor, J; Walker, B; Moorman, A; Russell, L
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/389762
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