ArticleBlood2022
Overcoming IMiD resistance in T-cell lymphomas through potent degradation of ZFP91 and IKZF1.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
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- miR-640 Enhances Abemaciclib Sensitivity by Suppressing CDK Inhibitor Resistance-Associated Genes in Breast Cancer Cells.Journal of cellular and molecular medicine · 2026Article
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- Molecular glue degraders: Rational design, specificity engineering, and advanced delivery.Acta pharmaceutica Sinica. B · 2026Review
- Genome-wide screening identifies ZFP91 as a key regulator of EVI1 in myeloid leukemia.Oncogene · 2026Article
- A phase 1 trial of romidepsin, azacitidine, dexamethasone, and lenalidomide in relapsed or refractory T-cell lymphoma.Blood advances · 2026Article
- A novel human acute myeloid leukemia cell line SDEY-AML1 with KMT2A: MLLT3, IKZF1: EVX1 fusions exhibits high tumorigenicity in NSG mice.Scientific reports · 2026Article
- Regulation of BCL11A DNA binding and expression in human erythrocyte precursor HUDEP-2 cells.bioRxiv : the preprint server for biology · 2026Article
- ZBTB11 depletion targets metabolic vulnerabilities in KRAS inhibitor-resistant PDAC.Nature chemical biology · 2026Article
- Six-Transmembrane Epithelial Antigen of the Prostate 1 Promotes HCC Proliferation and Metastasis in vitro and in vivo via the Wnt/β-Catenin Signaling Pathway.Cancer management and research · 2026Article
- Targeting the akt/mtor signaling pathway by maprotiline leads to tumor suppression in T-cell lymphoma.Annals of hematology · 2025Article
- Dual CARM1-and IKZF3-targeting: A novel approach to multiple myeloma therapy synergy between CARM1 inhibition and IMiDs.Molecular therapy. Oncology · 2025Article
- Predicting PROTAC off-target effects via warhead involvement levels in drug-target interactions using graph attention neural networks.Computational and structural biotechnology journal · 2025Article
- Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes.Journal of neuroinflammation · 2024Article
- Targeted protein degradation: advances in drug discovery and clinical practice.Signal transduction and targeted therapy · 2024Review
- Novel potent molecular glue degraders against broad range of hematological cancer cell lines via multiple neosubstrates degradation.Journal of hematology & oncology · 2024Article
- Article
- LILRB4 regulates multiple myeloma development through STAT3-PFKFB1 pathway.Cell death & disease · 2024Article
- MYC Inhibition Potentiates CD8+ T Cells Against Multiple Myeloma and Overcomes Immunomodulatory Drug Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Mezigdomide-A Novel Cereblon E3 Ligase Modulator under Investigation in Relapsed/Refractory Multiple Myeloma.Cancers · 2024Review
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Authors and funding
28 authors at 9 institutions in 4 countries.
Funding
Abstract
Immunomodulatory (IMiD) agents like lenalidomide and pomalidomide induce the recruitment of IKZF1 and other targets to the CRL4CRBN E3 ubiquitin ligase, resulting in their ubiquitination and degradation. These agents are highly active in B-cell lymphomas and a subset of myeloid diseases but have compromised effects in T-cell lymphomas (TCLs). Here, we show that 2 factors determine resistance to IMiDs among TCLs. First, limited CRBN expression reduces IMiD activity in TCLs but can be overcome by newer-generation degrader CC-92480. Using mass spectrometry, we show that CC-92480 selectively degrades IKZF1 and ZFP91 in TCL cells with greater potency than pomalidomide. As a result, CC-92480 is highly active against multiple TCL subtypes and showed greater efficacy than pomalidomide across 4 in vivo TCL models. Second, we demonstrate that ZFP91 functions as a bona fide transcription factor that coregulates cell survival with IKZF1 in IMiD-resistant TCLs. By activating keynote genes from WNT, NF-kB, and MAP kinase signaling, ZFP91 directly promotes resistance to IKZF1 loss. Moreover, lenalidomide-sensitive TCLs can acquire stable resistance via ZFP91 rewiring, which involves casein kinase 2-mediated c-Jun inactivation. Overall, these findings identify a critical transcription factor network within TCLs and provide clinical proof of concept for the novel therapy using next-generation degraders.
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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.