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December 8, 2025Blood

PHF19 inhibition increases IMiDs sensitivity by epigenetically regulating IRF4 and MYC in multiple myeloma

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Authors

XZXiaoyu ZhangLQLugui Qiu

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Overview

Experiments demonstrate PHF19 knockdown improves IMiD sensitivity in multiple myeloma, indicating epigenetic regulation of IRF4 and MYC pathways.

Key Points

  • This research aims to explore the role of PHF19 in drug resistance in multiple myeloma and its effect on IMiD sensitivity.
  • Performed RNA sequencing on primary CD138+ bone marrow mononuclear cells from MM patients
  • Conducted PHF19 knockdown to assess effects on cell proliferation and apoptosis
  • Utilized ATAC-seq to examine chromatin accessibility in PHF19-depleted cells
  • Measured IRF4 and MYC expression levels through RT-qPCR and Western blot
  • Assessed IMiD sensitivity using CCK-8 assays and flow cytometry.
  • PHF19 knockdown impaired MM cell proliferation and induced cell cycle arrest and apoptosis
  • Decreased levels of IRF4 and MYC were confirmed upon PHF19 depletion
  • Integrated analyses revealed reduced transcriptional accessibility at multiple gene loci
  • PHF19 depletion sensitized MM cells to IMiDs treatment
  • Targeting PHF19 enhances IMiD sensitivity, indicating its role in resistance mechanisms.

Cite This Study

Zhang et al. (2025) studied this question.

synapsesocial.com/papers/69362f5a4fa91c937236db83https://doi.org/10.1182/blood-2025-2164
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1PHF19 promotes multiple myeloma tumorigenicity through PRC2 activation and broad H3K27me3 domain formation2019 · 81 citations
  2. 21q amplification and PHF19 expressing high-risk cells are associated with relapsed/refractory multiple myeloma2024 · 6 citations
  3. 3Synergistic targeting of the ARID2–MYC axis by pomalidomide and panobinostat overcomes intrinsic IMiD resistance in multiple myeloma2026 · 1 citations
  4. 4Immunomodulatory drugs rewire mTORC1-dependent pathways in multiple myeloma to trigger cytotoxicity and immunogenic cell death2025
  5. 5MYC Inhibition Potentiates CD8+ T Cells Against Multiple Myeloma and Overcomes Immunomodulatory Drug Resistance2024 · 17 citations