ArticleBritish journal of haematology2014
Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.).
Article in British journal of haematology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05199311 (A Phase I/II Study of Carfilzomib, Iberdomide), which is not on this map. Cited by 338 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Phase I/II Study of Carfilzomib, Iberdomide (CC-220) and Dexamethasone (KID) in Patients With Newly Diagnosed Transplant Eligible Multiple Myeloma
Who cites it
338 citing papers in PubMed, 1 synthesis or guideline pooled it, 615 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- Clinical and immunological effects of adding cyclophosphamide to pomalidomide-dexamethasone in relapsed-refractory multiple myeloma: The randomized MUKseven trial.British journal of haematology · 2026Trial
- Six-month rituximab-lenalidomide regimen in advanced untreated follicular lymphoma: SAKK 35/10 trial 10-year update.Blood advances · 2025Trial
- Blockade of LAG-3 and PD-1 leads to co-expression of cytotoxic and exhaustion gene modules in CD8Cell · 2024Trial
- Pharmacodynamic changes in tumor and immune cells drive iberdomide's clinical mechanisms of activity in relapsed and refractory multiple myeloma.Cell reports. Medicine · 2024Trial
- Trial
- Association of proton pump inhibitor use with survival and adverse effects outcomes in patients with multiple myeloma: pooled analysis of three clinical trials.Scientific reports · 2024Trial
- Obinutuzumab-atezolizumab-lenalidomide for the treatment of patients with relapsed/refractory follicular lymphoma: final analysis of a Phase Ib/II trial.Blood cancer journal · 2021Trial
- Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial.Haematologica · 2021Trial
- First-in-Human, Single- and Multiple-Ascending-Dose Studies in Healthy Subjects to Assess Pharmacokinetics, Pharmacodynamics, and Safety/Tolerability of Iberdomide, a Novel Cereblon E3 Ligase Modulator.Clinical pharmacology in drug development · 2021Trial
- Trial
- Trial
- Analysis of Japanese patients from the AUGMENT phase III study of lenalidomide + rituximab (RInternational journal of hematology · 2020Trial
- Altretamine induces ferroptosis in small cell lung cancer by promoting epigenetic silencing and lysosomal degradation of GPX4.British journal of cancer · 2026Article
- Paraneoplastic pemphigus associated with follicular lymphoma and myasthenia gravis: Efficacy of a lenalidomide-rituximab-corticosteroid regimen.JAAD case reports · 2026Article
- The synthetic landscape of cereblon (CRBN) binders: from thalidomide to emerging chemotypes.Chemical Society reviews · 2026Review
- Molecular glue degraders: Rational design, specificity engineering, and advanced delivery.Acta pharmaceutica Sinica. B · 2026Review
- Advances in immune microenvironment profiling during multiple myeloma progression and therapy.International journal of hematology · 2026Review
- Review
- Cereblon induces G3BP2 neosubstrate degradation using molecular surface mimicry.Nature structural & molecular biology · 2026Article
278 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
15 authors at 2 institutions in 2 countries.
Funding
Abstract
Cereblon (CRBN), the molecular target of lenalidomide and pomalidomide, is a substrate receptor of the cullin ring E3 ubiquitin ligase complex, CRL4(CRBN) . T cell co-stimulation by lenalidomide or pomalidomide is cereblon dependent: however, the CRL4(CRBN) substrates responsible for T cell co-stimulation have yet to be identified. Here we demonstrate that interaction of the transcription factors Ikaros (IKZF1, encoded by the IKZF1 gene) and Aiolos (IKZF3, encoded by the IKZF3 gene) with CRL4(CRBN) is induced by lenalidomide or pomalidomide. Each agent promotes Aiolos and Ikaros binding to CRL4(CRBN) with enhanced ubiquitination leading to cereblon-dependent proteosomal degradation in T lymphocytes. We confirm that Aiolos and Ikaros are transcriptional repressors of interleukin-2 expression. The findings link lenalidomide- or pomalidomide-induced degradation of these transcriptional suppressors to well documented T cell activation. Importantly, Aiolos could serve as a proximal pharmacodynamic marker for lenalidomide and pomalidomide, as healthy human subjects administered lenalidomide demonstrated Aiolos degradation in their peripheral T cells. In conclusion, we present a molecular model in which drug binding to cereblon results in the interaction of Ikaros and Aiolos to CRL4(CRBN) , leading to their ubiquitination, subsequent proteasomal degradation and T cell activation.
Indexed as
Identifiers
What OpenQuestion holds
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.