ArticleBlood2010
Influence of bone marrow stromal microenvironment on forodesine-induced responses in CLL primary cells.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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.
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Who cites it
32 citing papers in PubMed, 64 citations in OpenAlex.
- A phase I-II trial of fludarabine, bendamustine and rituximab (FBR) in previously treated patients with CLL.Oncotarget · 2017Trial
- Preclinical and clinical evaluation of forodesine in pediatric and adult B-cell acute lymphoblastic leukemia.Clinical lymphoma, myeloma & leukemia · 2013Trial
- Trial
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- AR expression-independent XRCC3 mediates DNA damage-induced p53/Bax signaling pathway activation against prostate cancer.Journal of cancer research and clinical oncology · 2024Article
- Long non-coding RNAJournal of thoracic disease · 2023Article
- The role of extracellular vesicles in cholangiocarcinoma tumor microenvironment.Frontiers in pharmacology · 2023Review
- Mesenchymal stem cells in cancer progression and anticancer therapeutic resistance.Cancer cell international · 2021Review
- Mesenchymal stem cells in cancer therapy; the art of harnessing a foe to a friend.Iranian journal of basic medical sciences · 2021Review
- Importance of the origin of mesenchymal (stem) stromal cells in cancer biology: "alliance" or "war" in intercellular signals.Cell & bioscience · 2021Review
- Mesenchymal stem cells as a double-edged sword in tumor growth: focusing on MSC-derived cytokines.Cellular & molecular biology letters · 2021Review
- Bioinspired Extracellular Vesicles: Lessons Learned From Nature for Biomedicine and Bioengineering.Nanomaterials (Basel, Switzerland) · 2020Review
- Role of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Epithelial-Mesenchymal Transition.International journal of molecular sciences · 2019Review
- Biological and metabolic effects of IACS-010759, an OxPhos inhibitor, on chronic lymphocytic leukemia cells.Oncotarget · 2018Article
- Distinct protein signatures of acute myeloid leukemia bone marrow-derived stromal cells are prognostic for patient survival.Haematologica · 2018Article
- Macrophages confer survival signals via CCR1-dependent translational MCL-1 induction in chronic lymphocytic leukemia.Oncogene · 2017Article
- Extracellular vesicles as regulators of tumor fate: crosstalk among cancer stem cells, tumor cells and mesenchymal stem cells.Stem cell investigation · 2017Review
- Mesenchymal stem cells as a double-edged sword in suppression or progression of solid tumor cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.Oncotarget · 2016Article
- Reactivation of Smac-mediated apoptosis in chronic lymphocytic leukemia cells: mechanistic studies of Smac mimetic.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Forodesine, a purine nucleoside phosphorylase inhibitor, displays in vitro activity in chronic lymphocytic leukemia (CLL) cells in presence of dGuo, which is the basis for an ongoing clinical trial in patients with fludarabine-refractory CLL. Initial clinical data indicate forodesine has significant activity on circulating CLL cells, but less activity in clearing CLL cells from tissues such as marrow. In tissue microenvironments, lymphocytes interact with accessory stromal cells that provide survival and drug-resistance signals, which may account for residual disease. Therefore, we investigated the impact of marrow stromal cells (MSCs) on forodesine-induced response in CLL lymphocytes. We demonstrate that spontaneous and forodesine-induced apoptosis of CLL cells was significantly inhibited by human and murine MSCs. Forodesine-promoted dGuo triphosphate (dGTP) accumulation and GTP and ATP depletion in CLL cells was inhibited by MSCs, providing a mechanism for resistance. Also, MSCs rescued CLL cells from forodesine-induced RNA- and protein-synthesis inhibition and stabilized and increased Mcl-1 transcript and protein levels. Conversely, MSC viability was not affected by forodesine and dGuo. Collectively, MSC-induced biochemical changes antagonized forodesine-induced CLL cell apoptosis. This provides a biochemical mechanism for MSC-derived resistance to forodesine and emphasizes the need to move toward combinations with agents that interfere with the microenvironment's protective role for improving current therapeutic efforts.
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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.