ArticleBlood2014
Lenalidomide inhibits the proliferation of CLL cells via a cereblon/p21(WAF1/Cip1)-dependent mechanism independent of functional p53.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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.
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
43 citing papers in PubMed, 85 citations in OpenAlex.
- Trial
- Early Intervention with Lenalidomide in Patients with High-risk Chronic Lymphocytic Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Lenalidomide plus bendamustine-rituximab does not overcome the adverse impact ofHaematologica · 2018Trial
- Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia.Journal of immunology (Baltimore, Md. : 1950) · 2018Trial
- Lenalidomide consolidation benefits patients with CLL receiving chemoimmunotherapy: results for CALGB 10404 (Alliance).Blood advances · 2018Trial
- Lenalidomide treatment and prognostic markers in relapsed or refractory chronic lymphocytic leukemia: data from the prospective, multicenter phase-II CLL-009 trial.Blood cancer journal · 2016Trial
- Targeted degradation of USP7 in solid cancer cells reveals distinct effects of deubiquitinase degraders and inhibitors.Nature communications · 2026Article
- Tumor microenvironment as a novel therapeutic target for lymphoid leukemias.Annals of hematology · 2025Review
- IKAROS: from chromatin organization to transcriptional elongation control.Cell death and differentiation · 2025Review
- Tumor Cell Survival Factors and Angiogenesis in Chronic Lymphocytic Leukemia: How Hot Is the Link?Cancers · 2024Review
- Obinutuzumab, High-Dose Methylprednisolone (HDMP), and Lenalidomide for the Treatment of Patients with Richter's Syndrome.Cancers · 2022Article
- Review
- Catchet-MS identifies IKZF1-targeting thalidomide analogues as novel HIV-1 latency reversal agents.Nucleic acids research · 2022Article
- Reshaping the tumor microenvironment: The versatility of immunomodulatory drugs in B-cell neoplasms.Frontiers in immunology · 2022Review
- Cereblon: promise and challenges for combating human diseases.Pflugers Archiv : European journal of physiology · 2021Review
- Role of lenalidomide in the treatment of peripheral T-cell non-Hodgkin lymphomas.World journal of clinical oncology · 2021Review
- Altered DNA Methylation Profiles inInternational journal of molecular sciences · 2021Article
- Immunomodulatory Drugs for the Treatment of B Cell Malignancies.International journal of molecular sciences · 2021Review
- IRF4 modulates the response to BCR activation in chronic lymphocytic leukemia regulating IKAROS and SYK.Leukemia · 2021Article
- Article
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12 authors at 1 institution in 1 country.
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Abstract
Lenalidomide has demonstrated clinical activity in patients with chronic lymphocytic leukemia (CLL), even though it is not cytotoxic for primary CLL cells in vitro. We examined the direct effect of lenalidomide on CLL-cell proliferation induced by CD154-expressing accessory cells in media containing interleukin-4 and -10. Treatment with lenalidomide significantly inhibited CLL-cell proliferation, an effect that was associated with the p53-independent upregulation of the cyclin-dependent kinase inhibitor, p21(WAF1/Cip1) (p21). Silencing p21 with small interfering RNA impaired the capacity of lenalidomide to inhibit CLL-cell proliferation. Silencing cereblon, a known molecular target of lenalidomide, impaired the capacity of lenalidomide to induce expression of p21, inhibit CD154-induced CLL-cell proliferation, or enhance the degradation of Ikaros family zinc finger proteins 1 and 3. We isolated CLL cells from the blood of patients before and after short-term treatment with low-dose lenalidomide (5 mg per day) and found the leukemia cells were also induced to express p21 in vivo. These results indicate that lenalidomide can directly inhibit proliferation of CLL cells in a cereblon/p21-dependent but p53-independent manner, at concentrations achievable in vivo, potentially contributing to the capacity of this drug to inhibit disease-progression in patients with CLL.
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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.