ArticleBlood2010
Lenalidomide treatment promotes CD154 expression on CLL cells and enhances production of antibodies by normal B cells through a PI3-kinase-dependent pathway.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00466895 (Phase I Study of Lenalidomide in Acute Leukemias and Chronic Lymphocytic Leukemia.), which is not on this map. Cited by 49 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.
Phase I Study of Lenalidomide in Acute Leukemias and Chronic Lymphocytic Leukemia.
Who cites it
49 citing papers in PubMed, 117 citations in OpenAlex.
- 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
- Efficacy and predictors of response of lenalidomide and rituximab in patients with treatment-naive and relapsed CLL.Blood advances · 2019Trial
- 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
- Trial
- Lenalidomide induces long-lasting responses in elderly patients with chronic lymphocytic leukemia.Blood · 2013Trial
- Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2013Trial
- Trial
- Single-agent lenalidomide in the treatment of previously untreated chronic lymphocytic leukemia.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2011Trial
- A causal inference framework for identifying essential genes to enhance drug synergy prediction.Bioinformatics (Oxford, England) · 2026Article
- ROR1: an orphan becomes apparent.Blood · 2022Review
- Reshaping the tumor microenvironment: The versatility of immunomodulatory drugs in B-cell neoplasms.Frontiers in immunology · 2022Review
- Can Immunocompetence Be Restored in Chronic Lymphocytic Leukemia?Hematology/oncology clinics of North America · 2021Review
- Modulation of immune checkpoint molecule expression in mantle cell lymphoma.Leukemia & lymphoma · 2019Article
- Nfatc4 Deficiency Attenuates Ototoxicity by Suppressing Tnf-Mediated Hair Cell Apoptosis in the Mouse Cochlea.Frontiers in immunology · 2019Article
- Sustained long-lasting responses after lenalidomide discontinuation in patients with chronic lymphocytic leukemia.Leukemia · 2018Article
- Lenalidomide, Thalidomide, and Pomalidomide Reactivate the Epstein-Barr Virus Lytic Cycle through Phosphoinositide 3-Kinase Signaling and Ikaros Expression.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Lenalidomide Induces Interleukin-21 Production by T Cells and Enhances IL21-Mediated Cytotoxicity in Chronic Lymphocytic Leukemia B Cells.Cancer immunology research · 2016Article
- Low dose of lenalidmide and PI3K/mTOR inhibitor trigger synergistic cytoxicity in activated B cell-like subtype of diffuse large B cell lymphoma.Journal of experimental & clinical cancer research : CR · 2016Article
- Microenvironment interactions and B-cell receptor signaling in Chronic Lymphocytic Leukemia: Implications for disease pathogenesis and treatment.Biochimica et biophysica acta · 2016Review
- A balancing act: orchestrating amino-truncated and full-length p73 variants as decisive factors in cancer progression.Oncogene · 2015Review
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Chronic lymphocytic leukemia (CLL) involves a profound humoral immune defect and tumor-specific humoral tolerance that directly contribute to disease morbidity and mortality. CD154 gene therapy can reverse this immune defect, but attempts to do this pharmacologically have been unsuccessful. The immune-modulatory agent lenalidomide shows clinical activity in CLL, but its mechanism is poorly understood. Here, we demonstrate that lenalidomide induces expression of functional CD154 antigen on CLL cells both in vitro and in vivo. This occurs via enhanced CD154 transcription mediated by a Nuclear Factor of Activated T cells c1 (NFATc1)/Nuclear Factor-kappaB (NF-kappaB) complex and also through phosphoinositide-3 (PI3)-kinase pathway-dependent stabilization of CD154 mRNA. Importantly, CD154-positive CLL cells up-regulate BID, DR5, and p73, become sensitized to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis, and promote costimulatory activation of normal B cells to produce antibodies. In CLL patients receiving lenalidomide, similar evidence of CD154 activation is observed including BID, DR5, and p73 induction and also development of anti-ROR1 tumor-directed antibodies. Our data demonstrate that lenalidomide promotes CD154 expression on CLL cells with subsequent activation phenotype, and may therefore reverse the humoral immune defect observed in this disease. This study is registered at http://clinicaltrials.gov as NCT00466895.
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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.