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

Author

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

Abstract

Rarely, immunophenotypically immature B-cell precursor acute lymphoblastic leukemia (BCP-ALL) carries an immunoglobulin-MYC rearrangement (IG-MYC-r). This can result in diagnostic confusion with Burkitt lymphoma/leukemia and use of individualized treatment schedules of unproven efficacy. Here we compare the molecular characteristics of these conditions and investigate historic clinical outcome data. We identified 90 cases registered in a national BCP-ALL clinical trial/registry. When present, diagnostic material underwent cytogenetic, exome, methylome and transcriptome analyses. The outcomes analyzed were 3-year event-free survival and overall survival. 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-ABL1, 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 leukemia/lymphoma. Children with IG-MYC-r within that subgroup had a 3-year event-free survival of 47% and overall survival of 60%, representing a high-risk BCP-ALL. To develop effective management strategies this group of patients must be allowed access to contemporary, minimal residual disease-adapted, prospective clinical trial protocols.

Published
2023

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

Author

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

Published
2022
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4. A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-Cell Non-Hodgkin Lymphoma (Glo-BNHL)

Author

Seaford, Emma, Maycock, Shanna, Alexander, Sarah, Beishuizen, Auke, Wistinghausen, Birte, Minard-Colin, Veronique, Rigaud, Charlotte, Phillips, Charles A, Ford, James B., Kearns, Pamela R., Lawson, Anna, Williams, Ellie, Ahmed, Zahra, Muzaffar, Mahnoor, Parsons, Rhianna, Gore, Lia, Scobie, Nicole, Buenger, Victoria, Allen, Carl, Mellgren, Karin, Bollard, Catherine M., Auperin, Anne, Billingham, Lucinda, and Burke, Gladstone Austin Amos

Published
2023
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5. A Potential Paradigm for the Robust and Systematic Prioritisation of Assets in Academic-Led, Multi-Industry Collaborative Trials in Rare Populations (Glo-BNHL)

Author

Seaford, Emma, Scobie, Nicole, Gore, Lia, Alexander, Sarah, Beishuizen, Auke, Wistinghausen, Birte, Minard-Colin, Veronique, Bollard, Catherine M., Mellgren, Karin, Allen, Carl, Auperin, Anne, Buenger, Victoria, Kearns, Pamela R., Lawson, Anna, Williams, Ellie, Maycock, Shanna, Ahmed, Zahra, Muzaffar, Mahnoor, Parsons, Rhianna, Billingham, Lucinda, and Burke, Gladstone Austin Amos

Published
2023
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6. Molecular characterization and clinical outcome of B-cell precursor acute lymphoblastic leukemia with IG-MYC rearrangement.

Author

Bomken S, Enshaei A, Schwalbe EC, Mikulasova A, Dai Y, Zaka M, Fung KTM, Bashton M, Lim H, Jones L, Karataraki N, Winterman E, Ashby C, Attarbaschi A, Bertrand Y, Bradtke J, Buldini B, Burke GAA, Cazzaniga G, Gohring G, De Groot-Kruseman HA, Haferlach C, Nigro LL, Parihar M, Plesa A, Seaford E, Sonneveld E, Strehl S, Van der Velden VHJ, Rand V, Hunger SP, Harrison CJ, Bacon CM, Van Delft FW, Loh ML, Moppett J, Vormoor J, Walker BA, Moorman AV, and Russell LJ

Subjects
Child, Humans, Prospective Studies, Immunoglobulins genetics, Gene Rearrangement, Burkitt Lymphoma diagnosis, Burkitt Lymphoma genetics, Burkitt Lymphoma therapy, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma therapy
Abstract

Rarely, immunophenotypically immature B-cell precursor acute lymphoblastic leukemia (BCP-ALL) carries an immunoglobulin- MYC rearrangement (IG-MYC-r). This can result in diagnostic confusion with Burkitt lymphoma/leukemia and use of individualized treatment schedules of unproven efficacy. Here we compare the molecular characteristics of these conditions and investigate historic clinical outcome data. We identified 90 cases registered in a national BCP-ALL clinical trial/registry. When present, diagnostic material underwent cytogenetic, exome, methylome and transcriptome analyses. The outcomes analyzed were 3-year event-free survival and overall survival. 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-ABL1, 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 leukemia/lymphoma. Children with IG-MYC-r within that subgroup had a 3-year event-free survival of 47% and overall survival of 60%, representing a high-risk BCP-ALL. To develop effective management strategies this group of patients must be allowed access to contemporary, minimal residual disease-adapted, prospective clinical trial protocols.

Published
2023
Full Text
View/download PDF

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