ArticleBlood cancer journal2019
Identification of lenalidomide resistance pathways in myeloma and targeted resensitization using cereblon replacement, inhibition of STAT3 or targeting of IRF4.
Article in Blood cancer journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
67 citing papers in PubMed, 93 citations in OpenAlex.
- Trial
- Activating RARβ to overcome immunomodulatory drug resistance in t(4;14) human myeloma.Leukemia · 2026Article
- Understanding and addressing resistance to IMiDs immunomodulatory compounds in multiple myeloma.The FEBS journal · 2026Review
- Multiple myeloma: A tale of deregulated transcription factors.HemaSphere · 2026Review
- A bibliometric analysis of the research landscape of lenalidomide resistance in multiple myeloma.Discover oncology · 2026Article
- Pharmacological targeting of IRF4 as a therapeutic strategy for multiple myeloma.Nature chemical biology · 2026Article
- Targeting PRKCN, an Essential Driver Orchestrating mTOR-IRF4 Axis Independently of Kinase Activity, in Multiple Myeloma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Art of Domesticating Proteins: How Cancer Cells Adapt to Therapeutic and Environmental Stressors.International journal of molecular sciences · 2026Review
- Catalytic Inhibition of p300 Preferentially Targets IRF4 Oncogenic Activity and Tumor Growth in Multiple Myeloma.Cancer research · 2026Article
- Article
- Cancer degronopathies and protein-fate biomarkers in drug resistance and cancer progression: signalling mechanisms, measurement and translational limits.Frontiers in cell and developmental biology · 2026Review
- Reduced ALDH1A1 expression in multiple myeloma cells increases resistance to daratumumab via downregulation of retinoic acid.Cellular and molecular life sciences : CMLS · 2025Article
- A novel cereblon variant with both exon 8 and 10 deletions in newly diagnosed and relapsed multiple myeloma.Blood neoplasia · 2025Article
- Resistance to immunomodulatory drugs in multiple myeloma: the cereblon pathway and beyond.Haematologica · 2025Review
- Dual CARM1-and IKZF3-targeting: A novel approach to multiple myeloma therapy synergy between CARM1 inhibition and IMiDs.Molecular therapy. Oncology · 2025Article
- Article
- Immunocompetent mouse models of multiple myeloma.Seminars in hematology · 2025Review
- Novel Therapies in Primary Central Nervous System Lymphoma.Clinical pharmacology : advances and applications · 2025Review
- Activated PRDM1-CREBBP contributes to preeclampsia by regulating apoptosis and invasion of the human trophoblast cells.iScience · 2024Article
- Novel potent molecular glue degraders against broad range of hematological cancer cell lines via multiple neosubstrates degradation.Journal of hematology & oncology · 2024Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
To understand immunomodulatory drug (IMiD) resistance in multiple myeloma (MM), we created isogenic human multiple myeloma cell lines (HMCLs) sensitive and resistant to lenalidomide, respectively. Four HMCLs were demonstrated to be resistant to all IMiDs including lenalidomide, pomalidomide, and CC-220, but not to Bortezomib. In three HMLCs (MM.1.SLenRes, KMS11LenRes and OPM2LenRes), CRBN abnormalities were found, including chromosomal deletion, point mutation, and low CRBN expression. The remaining HMCL, XG1LenRes, showed no changes in CRBN but exhibited CD147 upregulation and impaired IRF4 downregulation after lenalidomide treatment. Depletion of CD147 in XG1LenRes and three additional HMCLs had no significant impact on MM viability and lenalidomide response. Further analysis of XG1LenRes demonstrated increased IL6 expression and constitutive STAT3 activation. Inhibition of STAT3 with a selective compound (PB-1-102) re-sensitized XG1LenRes to lenalidomide. Since XG1LenRes harbors a truncated IRF4 that is not downregulated by lenalidomide, we targeted IRF4/MYC axis with a selective inhibitor of the bromodomain of CBP/EP300 (SGC-CBP30), which restored lenalidomide response in XG1LenRes. This strategy also appeared to be more broadly applicable as SGC-CBP30 could re-sensitize two resistant HMCLs with low but detectable CRBN expression to lenalidomide, suggesting that targeting CBP/E300 is a promising approach to restore IMiD sensitivity in MM with detectable CRBN expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.