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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
IGH::CD274 (PD-L1) rearrangement in diffuse large B cell lymphoma and its therapeutic implication
Xuemei Wu1, Si Chen2, Ping Chen1
1Department of Hematology Second Affiliated Hospital of Soochow University Suzhou China.
Insights
Diffuse large B cell lymphoma (DLBCL) with high programmed death ligand 1 (PD-L1) expression, often resistant to standard therapy, can be caused by IGH::PD-L1 rearrangements. These patients may benefit from PD-1 inhibitors combined with R-CHOP therapy.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Diffuse large B cell lymphoma (DLBCL) frequently overexpresses programmed death ligand 1 (PD-L1), a mechanism that protects tumor cells from immune surveillance via the PD-L1/PD-1 pathway.
- Mechanisms contributing to PD-L1 overexpression include 3'end deletions of the PD-L1 gene, enhancing mRNA stability, and gene amplification.
- Prior research identified two DLBCL cases with an IGH::PD-L1 fusion, detected through whole genome sequencing.
Purpose of the Study:
- To report two additional cases of DLBCL with IGH::PD-L1 fusion.
- To highlight the utility of targeted DNA next-generation sequencing (NGS) in detecting IGH rearrangements.
- To investigate the therapeutic implications of PD-L1 overexpression in DLBCL.
Main Methods:
- Targeted DNA next-generation sequencing (NGS) was employed to detect IGH rearrangements.
- Clinical data from two DLBCL patients with identified IGH::PD-L1 fusions were analyzed.
- Treatment responses to standard R-CHOP chemotherapy and combination therapy with a PD-1 inhibitor were assessed.
Main Results:
- Two new cases of DLBCL harboring an IGH::PD-L1 fusion were identified using targeted DNA NGS.
- These genetic alterations lead to significant PD-L1 overexpression.
- Patients with PD-L1 overexpressing DLBCL, previously noted for resistance to R-CHOP, showed positive responses to combined R-CHOP and PD-1 inhibitor treatment.
Conclusions:
- IGH::PD-L1 fusion is a recurrent mechanism driving PD-L1 overexpression in DLBCL.
- Targeted NGS is an effective method for detecting IGH rearrangements in DLBCL.
- Combination therapy involving PD-1 inhibitors offers a promising treatment strategy for DLBCL patients with PD-L1 overexpression.
Abstract:
Diffuse large B cell lymphoma (DLBCL) expresses abundant programmed death ligand 1 (PD-L1), which shields tumor cells from immune attacks through the PD-L1/PD-1 signaling axis. The mechanism of PD-L1 overexpression includes the deletion of the 3'end of PD-L1, which increases its mRNA stability, and the gain or amplification of PD-L1. Previous studies found two cases of DLBCL carrying an IGH::PD-L1 by whole genome sequencing. We describe two more such cases by a targeted DNA next-generation sequencing (NGS) capable of detecting IGH rearrangements, leading to PD-L1 overexpression. DLBCL with PD-L1 overexpression is often resistant to R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisolone). Our patients responded to a combination of R-CHOP and a PD-1 inhibitor.
