TY - JOUR
T1 - Molecular characterization and clinical outcome of B-cell precursor acute lymphoblastic leukemia with IG-MYC rearrangement
AU - Bomken, Simon
AU - Enshaei, Amir
AU - Schwalbe, Edward C.
AU - Mikulasova, Aneta
AU - Dai, Yunfeng
AU - Zaka, Masood
AU - Fung, Kent T.M.
AU - Bashton, Matthew
AU - Lim, Huezin
AU - Jones, Lisa
AU - Karataraki, Nefeli
AU - Winterman, Emily
AU - Ashby, Cody
AU - Attarbaschi, Andishe
AU - Bertrand, Yves
AU - Bradtke, Jutta
AU - Buldini, Barbara
AU - Burke, G. A.Amos
AU - Cazzaniga, Giovanni
AU - Göhring, Gudrun
AU - de Groot-Kruseman, Hesta A.
AU - Haferlach, Claudia
AU - Nigro, Luca Lo
AU - Parihar, Mayur
AU - Plesa, Adriana
AU - Seaford, Emma
AU - Sonneveld, Edwin
AU - Strehl, Sabine
AU - van der Velden, Vincent H.J.
AU - Rand, Vikki
AU - Hunger, Stephen P.
AU - Harrison, Christine J.
AU - Bacon, Chris M.
AU - van Delft, Frederik W.
AU - Loh, Mignon L.
AU - Moppett, John
AU - Vormoor, Josef
AU - Walker, Brian A.
AU - Moorman, Anthony V.
AU - Russell, Lisa J.
N1 - Publisher Copyright:
©2023 Ferrata Storti Foundation.
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85149153876&partnerID=8YFLogxK
U2 - 10.3324/haematol.2021.280557
DO - 10.3324/haematol.2021.280557
M3 - Article
C2 - 35484682
AN - SCOPUS:85149153876
SN - 0390-6078
VL - 108
SP - 717
EP - 731
JO - Haematologica
JF - Haematologica
IS - 3
ER -