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B-cell Receptor Silencing Reveals the Origin and Dependencies of High-Grade B-cell Lymphomas with MYC and BCL2 Rearrangements

22 May 2025

Abstract excerpt

The B-cell receptor (BCR) is critical for mature B-cell lymphomas (BCL), serving as a therapeutic target. We show that high-grade BCLs with MYC and BCL2 rearrangements [HGBCL-double-hit (DH)-BCL2] predominantly exhibit immunoglobulin heavy (IGH) chain silencing, leading to BCR shutdown. IGH-silenced HGBCL-DH-BCL2 (IGHUND) tumors differ from IGH+ counterparts in germinal center (GC) zone programs, MYC expression,...

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PMID: 40402557
DOI: 10.1158/2643-3230.bcd-25-0099

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