IGH::CD274 (PD-L1) rearrangement in diffuse large B cell lymphoma and its therapeutic implication

EJHaem. 2023 Apr 25;4(2):442-445. doi: 10.1002/jha2.693. eCollection 2023 May.

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.

Keywords: DLBCL; IGH; PDL1.