ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Stromal endothelial cells establish a bidirectional crosstalk with chronic lymphocytic leukemia cells through the TNF-related factors BAFF, APRIL, and CD40L.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 81 citations in OpenAlex.
- B-cell maturation antigen expression across hematologic cancers: a systematic literature review.Blood cancer journal · 2020Pooled it
- Pooled it
- Ibrutinib therapy downregulates AID enzyme and proliferative fractions in chronic lymphocytic leukemia.Blood · 2019Trial
- Cells, cytokines, chemokines, and cancer stress: A biobehavioral study of patients with chronic lymphocytic leukemia.Cancer · 2018Trial
- Integrated Network and Transcriptomic Analyses Identify a Candidate Ethanol-ADAM17 Molecular Axis Associated with Glioblastoma Progression.International journal of molecular sciences · 2026Article
- Genomic profile of an IDH-wild-type glioblastoma diagnosed following TNF-α inhibitor therapy: a molecular case study.Frontiers in oncology · 2026Article
- Immunomodulatory effects of BAFF and APRIL cytokines in post-pulmonary infection lung cancer: Implications for drug resistance and progression.Saudi medical journal · 2024Review
- Endothelial cells in tumor microenvironment: insights and perspectives.Frontiers in immunology · 2024Review
- An unappreciated cell survival-independent role for BAFF initiating chronic lymphocytic leukemia.Frontiers in immunology · 2024Article
- The Role of the Microenvironment and Cell Adhesion Molecules in Chronic Lymphocytic Leukemia.Cancers · 2023Review
- Exploring the crosstalk between endothelial cells, immune cells, and immune checkpoints in the tumor microenvironment: new insights and therapeutic implications.Cell death & disease · 2023Review
- Review
- Review
- The BAFF-APRIL System in Cancer.Cancers · 2023Review
- Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine.Frontiers in immunology · 2022Article
- CD160 receptor in CLL: Current state and future avenues.Frontiers in immunology · 2022Review
- Immunomodulatory Drugs for the Treatment of B Cell Malignancies.International journal of molecular sciences · 2021Review
- CD4+ T cells sustain aggressive chronic lymphocytic leukemia in Eμ-TCL1 mice through a CD40L-independent mechanism.Blood advances · 2021Article
- IFNγ, and to a Lesser Extent TNFα, Provokes a Sustained Endothelial Costimulatory Phenotype.Frontiers in immunology · 2021Article
- The PKN1- TRAF1 signaling axis as a potential new target for chronic lymphocytic leukemia.Oncoimmunology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Chronic lymphocytic leukemia (CLL) is a clonal B cell disorder of unknown origin. Accessory signals from the microenvironment are critical for the survival, expansion, and progression of malignant B cells. We found that the CLL stroma included microvascular endothelial cells (MVECs) expressing BAFF and APRIL, two TNF family members related to the T cell-associated B cell-stimulating molecule CD40L. Constitutive release of soluble BAFF and APRIL increased upon engagement of CD40 on MVECs by CD40L aberrantly expressed on CLL cells. In addition to enhancing MVEC expression of CD40, leukemic CD40L induced cleavases that elicited intracellular processing of pro-BAFF and pro-APRIL proteins in MVECs. The resulting soluble BAFF and APRIL proteins delivered survival, activation, Ig gene remodeling, and differentiation signals by stimulating CLL cells through TACI, BAFF-R, and BCMA receptors. BAFF and APRIL further amplified CLL cell survival by upregulating the expression of leukemic CD40L. Inhibition of TACI, BCMA, and BAFF-R expression on CLL cells; abrogation of CD40 expression in MVECs; or suppression of BAFF and APRIL cleavases in MVECs reduced the survival and diversification of malignant B cells. These data indicate that BAFF, APRIL, and CD40L form a CLL-enhancing bidirectional signaling network linking neoplastic B cells with the microvascular stroma.
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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.