ArticleLeukemia2004
A sustained activation of PI3K/NF-kappaB pathway is critical for the survival of chronic lymphocytic leukemia B cells.
Article in Leukemia, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
113 citing papers in PubMed, 236 citations in OpenAlex.
- Trial
- NOTCH and NF-κB interplay in chronic lymphocytic leukemia is independent of genetic lesion.International journal of hematology · 2013Trial
- Article
- Review
- Potential New Therapies "ROS-Based" in CLL: An Innovative Paradigm in the Induction of Tumor Cell Apoptosis.Antioxidants (Basel, Switzerland) · 2024Review
- The Role of Cholesterol in Chronic Lymphocytic Leukemia Development and Pathogenesis.Metabolites · 2023Review
- NF-kB and the CLL microenvironment.Frontiers in oncology · 2023Review
- Multiple Mechanisms of NOTCH1 Activation in Chronic Lymphocytic Leukemia: NOTCH1 Mutations and Beyond.Cancers · 2022Review
- miRNAs in Lymphocytic Leukaemias-The miRror of Drug Resistance.International journal of molecular sciences · 2022Review
- A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer.Cancers · 2022Review
- Targeting the Non-Canonical NF-κB Pathway in Chronic Lymphocytic Leukemia and Multiple Myeloma.Cancers · 2022Article
- The TKI Era in Chronic Leukemias.Pharmaceutics · 2021Review
- Molecular Action of Polyphenols in Leukaemia and Their Therapeutic Potential.International journal of molecular sciences · 2021Review
- HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia.Journal of translational medicine · 2021Article
- Constitutive activation of Lyn kinase enhances BCR responsiveness, but not the development of CLL in Eµ-TCL1 mice.Blood advances · 2020Article
- Responsiveness of chronic lymphocytic leukemia cells to B-cell receptor stimulation is associated with low expression of regulatory molecules of the nuclear factor-κB pathway.Haematologica · 2020Article
- Par-4 overexpression impedes leukemogenesis in the Eµ-TCL1 leukemia model through downregulation of NF-κB signaling.Blood advances · 2019Article
- Review
- CUDC-907 blocks multiple pro-survival signals and abrogates microenvironment protection in CLL.Journal of cellular and molecular medicine · 2019Article
- Role of long non-coding RNAs in disease progression of early stage unmutated chronic lymphocytic leukemia.Oncotarget · 2019Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The progressive rise of mature CD5+ B lymphocytes, despite the low proportion of proliferating cells, has led to the notion that B cell chronic lymphocytic leukemia (B-CLL) is primarily related to defective apoptosis. The microenvironment likely plays a prominent role because the malignant cells progressively accumulate in vivo, whereas they rapidly undergo spontaneous apoptosis when cultured in vitro. To assess microenvironment-mediated survival signals, B-CLL cells were cultured with a murine fibroblast cell line, Ltk-, with and without an agonistic antibody to CD40. Spontaneous apoptosis was associated with the loss of Akt and NF-kappaB activities. Interactions with fibroblasts sustained a basal level of Akt and NF-kappaB activities, which was dependent on phosphatidylinositol-3 kinase (PI3K). Constitutive activity of the PI3K pathway in B-CLL cells when cultured with fibroblasts prevented the downregulation of the prosurvival Bcl-2 family protein Bcl-xL and the caspase inhibitor proteins FLIPL and XIAP, and consequently caspase-3 activation and apoptosis. CD40 crosslinking in B-CLL cells did not further prevent murine fibroblasts-mediated apoptosis but induced cell proliferation, which was associated with an increase of Akt and NF-kappaB activation compared with cells cultured with fibroblasts alone. The PI3K pathway seems to play a pivotal role in B-CLL cell survival and growth.
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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.