ArticleLeukemia2019
RUNX proteins desensitize multiple myeloma to lenalidomide via protecting IKZFs from degradation.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 52 citations in OpenAlex.
- Understanding and addressing resistance to IMiDs immunomodulatory compounds in multiple myeloma.The FEBS journal · 2026Review
- Drug Resistance in Multiple Myeloma: Tumor-Intrinsic Mechanisms and the Bone Marrow Microenvironment.Cell biochemistry and function · 2026Review
- EZH2 inhibition overcomes immunomodulatory drug resistance in multiple myeloma via a cereblon-dependent pathway.Haematologica · 2026Article
- Multiple myeloma: A tale of deregulated transcription factors.HemaSphere · 2026Review
- Disrupting the CBFβ-SMMHC-RUNX1 oncogenic protein-protein interaction in inv(16) AML: from fusion biology to targeted therapy.Discover oncology · 2026Review
- RUNX proteins and CBFβ create an interconnected network of transcriptional regulation in the male germline†.Biology of reproduction · 2026Article
- Catalytic Inhibition of p300 Preferentially Targets IRF4 Oncogenic Activity and Tumor Growth in Multiple Myeloma.Cancer research · 2026Article
- RSK4 promotes the metastasis of clear cell renal cell carcinoma by activating RUNX1-mediated angiogenesis.Cancer biology & therapy · 2025Article
- Enhancer Extrachromosomal Circular DNA ANKRD28 Elicits Drug Resistance via POU2F2-Mediated Transcriptional Network in Multiple Myeloma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- SWI/SNF-type complexes-transcription factor interplay: a key regulatory interaction.Cellular & molecular biology letters · 2025Review
- IKAROS: from chromatin organization to transcriptional elongation control.Cell death and differentiation · 2025Review
- RUNX1 expression dynamics in plasma cell differentiation and pathogenesis of multiple myeloma.Frontiers in immunology · 2025Article
- A system-level model reveals that transcriptional stochasticity is required for hematopoietic stem cell differentiation.NPJ systems biology and applications · 2024Article
- LILRB4 regulates multiple myeloma development through STAT3-PFKFB1 pathway.Cell death & disease · 2024Article
- ETV4-Dependent Transcriptional Plasticity Maintains MYC Expression and Results in IMiD Resistance in Multiple Myeloma.Blood cancer discovery · 2024Article
- Article
- IMiD-Free Interval and IMiDs Sequence: Which Strategy Is Better Suited for Lenalidomide-Refractory Myeloma?Life (Basel, Switzerland) · 2023Review
- DLBCL-associated NOTCH2 mutations escape ubiquitin-dependent degradation and promote chemoresistance.Blood · 2023Article
- Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.Signal transduction and targeted therapy · 2023Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Ikaros family zinc finger protein 1 and 3 (IKZF1 and IKZF3) are transcription factors that promote multiple myeloma (MM) proliferation. The immunomodulatory imide drug (IMiD) lenalidomide promotes myeloma cell death via Cereblon (CRBN)-dependent ubiquitylation and proteasome-dependent degradation of IKZF1 and IKZF3. Although IMiDs have been used as first-line drugs for MM, the overall survival of refractory MM patients remains poor and demands the identification of novel agents to potentiate the therapeutic effect of IMiDs. Using an unbiased screen based on mass spectrometry, we identified the Runt-related transcription factor 1 and 3 (RUNX1 and RUNX3) as interactors of IKZF1 and IKZF3. Interaction with RUNX1 and RUNX3 inhibits CRBN-dependent binding, ubiquitylation, and degradation of IKZF1 and IKZF3 upon lenalidomide treatment. Inhibition of RUNXs, via genetic ablation or a small molecule (AI-10-104), results in sensitization of myeloma cell lines and primary tumors to lenalidomide. Thus, RUNX inhibition represents a valuable therapeutic opportunity to potentiate IMiDs therapy for the treatment of multiple myeloma.
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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.