ArticleThe Journal of clinical investigation2022
Epigenomic reprogramming via HRP2-MINA dictates response to proteasome inhibitors in multiple myeloma with t(4;14) translocation.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Activating RARβ to overcome immunomodulatory drug resistance in t(4;14) human myeloma.Leukemia · 2026Article
- Future of PARP inhibitors in cancer treatment: overcoming resistance and enhancing efficacy with combination therapies.Journal of Zhejiang University. Science. B · 2025Review
- Review
- ZMYND8 Reads H3K36me2 to Activate CEBPE Transcription and Suppress Multiple Myeloma Progression through the Inhibition of Adaptive UPR Pathways.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- HRP2 regulating MICU1-mediated CaNeoplasia (New York, N.Y.) · 2025Article
- Review
- Proteasome inhibition enhances the anti-leukemic efficacy of chimeric antigen receptor (CAR) expressing NK cells against acute myeloid leukemia.Journal of hematology & oncology · 2024Article
- Bone marrow stromal cells dictate lanosterol biosynthesis and ferroptosis of multiple myeloma.Oncogene · 2024Article
- Factors determining the sensitivity to proteasome inhibitors of multiple myeloma cells.Frontiers in pharmacology · 2024Review
- Deacetylation induced nuclear condensation of HP1γ promotes multiple myeloma drug resistance.Nature communications · 2023Article
- Characterization of Hepatoma-Derived Growth Factor-Related Protein 2 Interactions with Heterochromatin.Cells · 2023Article
- Molecular and immunological mechanisms of clonal evolution in multiple myeloma.Frontiers in immunology · 2023Review
- Ten Years of CRISPRing Cancers In Vitro.Cancers · 2022Review
- Article
- Deletion of mdig enhances H3K36me3 and metastatic potential of the triple negative breast cancer cells.iScience · 2022Article
- Review
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The chromosomal t(4;14) (p16;q32) translocation drives high expression of histone methyltransferase nuclear SET domain-containing 2 (NSD2) and plays vital roles in multiple myeloma (MM) evolution and progression. However, the mechanisms of NSD2-driven epigenomic alterations in chemoresistance to proteasome inhibitors (PIs) are not fully understood. Using a CRISPR/Cas9 sgRNA library in a bone marrow-bearing MM model, we found that hepatoma-derived growth factor 2 (HRP2) was a suppressor of chemoresistance to PIs and that its downregulation correlated with a poor response and worse outcomes in the clinic. We observed suppression of HRP2 in bortezomib-resistant MM cells, and knockdown of HRP2 induced a marked tolerance to PIs. Moreover, knockdown of HRP2 augmented H3K27me3 levels, consequentially intensifying transcriptome alterations promoting cell survival and restriction of ER stress. Mechanistically, HRP2 recognized H3K36me2 and recruited the histone demethylase MYC-induced nuclear antigen (MINA) to remove H3K27me3. Tazemetostat, a highly selective epigenetic inhibitor that reduces H3K27me3 levels, synergistically sensitized the anti-MM effects of bortezomib both in vitro and in vivo. Collectively, these results provide a better understanding of the origin of chemoresistance in patients with MM with the t(4;14) translocation and a rationale for managing patients with MM who have different genomic backgrounds.
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