ArticleLeukemia2011
The functional in vitro response to CD40 ligation reflects a different clinical outcome in patients with chronic lymphocytic leukemia.
Article in Leukemia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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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
24 citing papers in PubMed, 42 citations in OpenAlex.
- Trial
- Scaffold-free three-dimensional culture of chronic lymphocytic leukaemia preserves B-T-cell cross-talk and enables drug response profiling.British journal of haematology · 2026Article
- Dynamic stimulation promotes functional tissue-like organization of a 3D human lymphoid microenvironment model in vitro.Cell reports methods · 2025Article
- Disrupting pro-survival and inflammatory pathways with dimethyl fumarate sensitizes chronic lymphocytic leukemia to cell death.Cell death & disease · 2024Article
- Review
- Enhanced Costimulatory Signaling Improves CAR T-cell Effector Responses in CLL.Cancer research communications · 2022Article
- In Vitro and In Vivo Models of CLL-T Cell Interactions: Implications for Drug Testing.Cancers · 2022Review
- LINC00152 expression in normal and Chronic Lymphocytic Leukemia B cells.Hematological oncology · 2022Article
- CD4+ T cells sustain aggressive chronic lymphocytic leukemia in Eμ-TCL1 mice through a CD40L-independent mechanism.Blood advances · 2021Article
- Article
- Modeling the Leukemia MicroenviromentFrontiers in oncology · 2020Review
- Molecular Players in Hematologic Tumor Cell Trafficking.Frontiers in immunology · 2019Review
- CD40L/IL-4-stimulated CLL demonstrates variation in translational regulation of DNA damage response genes including ATM.Blood advances · 2018Article
- Microenvironment interactions and B-cell receptor signaling in Chronic Lymphocytic Leukemia: Implications for disease pathogenesis and treatment.Biochimica et biophysica acta · 2016Review
- Article
- Targeting the proliferative and chemoresistant compartment in chronic lymphocytic leukemia by inhibiting survivin protein.Leukemia · 2014Article
- The Nedd8-activating enzyme inhibitor MLN4924 thwarts microenvironment-driven NF-κB activation and induces apoptosis in chronic lymphocytic leukemia B cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- "Role of the B-cell receptor and the microenvironment in chronic lymphocytic leukemia''.Blood cancer journal · 2013Article
- CD137 is induced by the CD40 signal on chronic lymphocytic leukemia B cells and transduces the survival signal via NF-κB activation.PloS one · 2013Article
- TNFR-associated factor 2 deficiency in B lymphocytes predisposes to chronic lymphocytic leukemia/small lymphocytic lymphoma in mice.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malignant B lymphocytes from chronic lymphocytic leukemia (CLL) patients maintain the capacity to respond to CD40 ligation, among other microenvironmental stimuli. In this study, we show that (i) leukemic CLL cells stimulated with the soluble form of CD40L in vitro show differential responses in terms of upregulation of surface markers (CD95 and CD80) and induction of chemokines (CCL22 and CCL17) expression/secretion, and that (ii) these changes are mirrored by a distinct activation of intracellular signalling pathways including increase in IKKalpha/beta phosphorylation and upregulation of antiapoptotic proteins (BCL-2 and MCL-1). CLL patients can then be segregated into two distinct functional subsets. We defined the responsive subset of cases CD40L dependent, considering the capacity to respond as a sign of persistent need of this stimulation for the leukemic expansion. Conversely, we named the unresponsive cases CD40L independent, considering them less dependent on this microenvironmental signal, presumably because of a higher autonomous proliferative and survival potential. Importantly, we report that (iii) the two functional subsets show an opposite clinical outcome, with CD40L-independent cases having a shorter time to progression. This indicates that the functional differences observed in vitro may reflect a different leukemic potential in vivo likely responsible for a distinct clinical course.
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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.