ArticleBlood2021
miR-29 modulates CD40 signaling in chronic lymphocytic leukemia by targeting TRAF4: an axis affected by BCR inhibitors.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Investigating the prognostic value of non-coding RNAs in chronic lymphocytic leukemia: insights from a systematic review and meta-analysis.BMC cancer · 2025Pooled it
- Repression of miR-29 via MYC leads to increased CD40 signaling in transformed follicular lymphoma.Leukemia · 2026Trial
- Investigating autophagy and miRNAs as therapeutic targets in leukemia.Discover oncology · 2026Review
- RNA binding protein Sam68 promotes germinal center reaction and IgG response through regulation of miR29.Cellular and molecular life sciences : CMLS · 2026Article
- Casein kinase 1δ/ε inhibition suppresses CLL proliferation through cell-intrinsic and microenvironmental mechanisms.HemaSphere · 2026Article
- Hypoxia Signaling and Non-Coding RNAs: Regulatory Networks and Therapeutic Implications in Breast Cancer.Current issues in molecular biology · 2026Review
- The structure and functions of TRAF families and recent advances of TRAFs in leukemia.Frontiers in oncology · 2026Review
- Epigenetics in B-CLL.International journal of genomics · 2026Review
- The CD40-CD154 axis in transplantation: from immunobiology to therapeutic targeting.Frontiers in immunology · 2026Review
- The miRNA Landscape of Leukemia - Cellular Actions to Therapy through Molecular Mechanisms.Cell biochemistry and biophysics · 2025Review
- FoxO1 signaling in B cell malignancies and its therapeutic targeting.FEBS letters · 2025Review
- Unraveling the Epigenetic Landscape of Mature B Cell Neoplasia: Mechanisms, Biomarkers, and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Mechanisms of apoptosis-related non-coding RNAs in ovarian cancer: a narrative review.Apoptosis : an international journal on programmed cell death · 2025Review
- Recent insights and perspectives into the role of the miRNA‑29 family in innate immunity (Review).International journal of molecular medicine · 2025Review
- MicroRNA Profiling as a Predictive Indicator for Time to First Treatment in Chronic Lymphocytic Leukemia: Insights from the O-CLL1 Prospective Study.Non-coding RNA · 2024Article
- Early reappearance of intraclonal proliferative subpopulations in ibrutinib-resistant chronic lymphocytic leukemia.Leukemia · 2024Article
- Article
- Non-coding RNAs as therapeutic targets in cancer and its clinical application.Journal of pharmaceutical analysis · 2024Review
- Advances in epigenetic alterations of chronic lymphocytic leukemia: from pathogenesis to treatment.Clinical and experimental medicine · 2024Review
- MicroRNAs: Potential prognostic and theranostic biomarkers in chronic lymphocytic leukemia.EJHaem · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 5 institutions in 3 countries.
Funding
Abstract
B-cell receptor (BCR) signaling and T-cell interactions play a pivotal role in chronic lymphocytic leukemia (CLL) pathogenesis and disease aggressiveness. CLL cells can use microRNAs (miRNAs) and their targets to modulate microenvironmental interactions in the lymph node niches. To identify miRNA expression changes in the CLL microenvironment, we performed complex profiling of short noncoding RNAs in this context by comparing CXCR4/CD5 intraclonal cell subpopulations (CXCR4dimCD5bright vs CXCR4brightCD5dim cells). This identified dozens of differentially expressed miRNAs, including several that have previously been shown to modulate BCR signaling (miR-155, miR-150, and miR-22) but also other candidates for a role in microenvironmental interactions. Notably, all 3 miR-29 family members (miR-29a, miR-29b, miR-29c) were consistently down-modulated in the immune niches, and lower miR-29(a/b/c) levels associated with an increased relative responsiveness of CLL cells to BCR ligation and significantly shorter overall survival of CLL patients. We identified tumor necrosis factor receptor-associated factor 4 (TRAF4) as a novel direct target of miR-29s and revealed that higher TRAF4 levels increase CLL responsiveness to CD40 activation and downstream nuclear factor-κB (NF-κB) signaling. In CLL, BCR represses miR-29 expression via MYC, allowing for concurrent TRAF4 upregulation and stronger CD40-NF-κB signaling. This regulatory loop is disrupted by BCR inhibitors (bruton tyrosine kinase [BTK] inhibitor ibrutinib or phosphatidylinositol 3-kinase [PI3K] inhibitor idelalisib). In summary, we showed for the first time that a miRNA-dependent mechanism acts to activate CD40 signaling/T-cell interactions in a CLL microenvironment and described a novel miR-29-TRAF4-CD40 signaling axis modulated by BCR activity.
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.