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Updated: Aug 8, 2026
VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
Published on: December 28, 2015
Molecular characterization and clinical outcome of B-cell precursor acute lymphoblastic leukemia with IG-MYC
Simon Bomken1, Amir Enshaei2, Edward C Schwalbe3
1Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne. s.n.bomken@newcastle.ac.uk.
Insights
Immunophenotypically immature B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with an immunoglobulin-MYC rearrangement (IG-MYC-r) is a distinct high-risk group. These patients require access to current, minimal residual disease-adapted clinical trials for effective management.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Immunophenotypically immature B-cell precursor acute lymphoblastic leukemia (BCP-ALL) rarely presents with an immunoglobulin-MYC rearrangement (IG-MYC-r).
- This genetic aberration can lead to diagnostic challenges, mimicking Burkitt lymphoma/leukemia, and necessitates careful molecular characterization.
- Current treatment strategies for this specific BCP-ALL subtype are often based on unproven efficacy.
Purpose of the Study:
- To compare the molecular characteristics of IG-MYC-r BCP-ALL with Burkitt lymphoma/leukemia.
- To investigate the clinical outcomes of patients with IG-MYC-r BCP-ALL.
- To identify distinct molecular subgroups within IG-MYC-r BCP-ALL.
Main Methods:
- Analysis of 90 cases from a national BCP-ALL clinical trial/registry.
- Application of cytogenetic, exome, methylome, and transcriptome analyses on diagnostic material.
- Evaluation of 3-year event-free survival and overall survival data.
Main Results:
- IG-MYC-r was found in various cytogenetic contexts, including co-occurrence with known BCP-ALL abnormalities and BCL2/BCL6-rearrangements, or as the sole defining feature (64 cases).
- A subgroup of V(D)J-rearranged IG-MYC-r cases showed distinct DNA methylation profiles, differentiating them from Burkitt leukemia/lymphoma.
- Children in this distinct subgroup had a 3-year event-free survival of 47% and overall survival of 60%, classifying them as high-risk BCP-ALL.
Conclusions:
- IG-MYC-r BCP-ALL represents a high-risk leukemia that is molecularly distinct from Burkitt leukemia/lymphoma.
- Effective management requires enrollment of these patients into contemporary, minimal residual disease-adapted, prospective clinical trials.
- Further research into the specific molecular drivers and therapeutic vulnerabilities of this subgroup is warranted.
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.
