ArticleNeoplasia (New York, N.Y.)2014
Regulation of Mcl-1 expression in context to bone marrow stromal microenvironment in chronic lymphocytic leukemia.
Article in Neoplasia (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 32 citations in OpenAlex.
- Targeting CDK9 inhibits the growth of KMT2A-rearranged infant leukemia and demonstrates synergy with menin inhibition.Blood neoplasia · 2025Article
- Venetoclax dose escalation rapidly activates a BAFF/BCL-2 survival axis in chronic lymphocytic leukemia.Blood · 2024Article
- MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents.Journal of hematology & oncology · 2020Review
- AMG-176, an Mcl-1 Antagonist, Shows Preclinical Efficacy in Chronic Lymphocytic Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Repression of Mcl-1 expression by the CDC7/CDK9 inhibitor PHA-767491 overcomes bone marrow stroma-mediated drug resistance in AML.Scientific reports · 2018Article
- CXCR4- and BCR-triggered integrin activation in B-cell chronic lymphocytic leukemia cells depends on JAK2-activated Bruton's tyrosine kinase.Oncotarget · 2018Article
- Microenvironment-induced PIM kinases promote CXCR4-triggered mTOR pathway required for chronic lymphocytic leukaemia cell migration.Journal of cellular and molecular medicine · 2018Article
- Proteomics profiling identifies induction of caveolin-1 in chronic lymphocytic leukemia cells by bone marrow stromal cells.Leukemia & lymphoma · 2018Article
- Potent anti-leukemic activity of a specific cyclin-dependent kinase 9 inhibitor in mouse models of chronic lymphocytic leukemia.Oncotarget · 2018Article
- Biological and metabolic effects of IACS-010759, an OxPhos inhibitor, on chronic lymphocytic leukemia cells.Oncotarget · 2018Article
- Article
- Hematologic Tumor Cell Resistance to the BCL-2 Inhibitor Venetoclax: A Product of Its Microenvironment?Frontiers in oncology · 2018Review
- BCL2-Family Dysregulation in B-Cell Malignancies: From Gene Expression Regulation to a Targeted Therapy Biomarker.Frontiers in oncology · 2018Article
- B-cell Receptor Signaling Regulates Metabolism in Chronic Lymphocytic Leukemia.Molecular cancer research : MCR · 2017Article
- The Stromal Microenvironment Modulates Mitochondrial Oxidative Phosphorylation in Chronic Lymphocytic Leukemia Cells.Neoplasia (New York, N.Y.) · 2017Article
- Comparison of Acalabrutinib, A Selective Bruton Tyrosine Kinase Inhibitor, with Ibrutinib in Chronic Lymphocytic Leukemia Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Idelalisib and bendamustine combination is synergistic and increases DNA damage response in chronic lymphocytic leukemia cells.Oncotarget · 2017Article
- Initial analysis of peripheral lymphocytic extracellular signal related kinase activation in autism.Journal of psychiatric research · 2017Article
- Reactivation of Smac-mediated apoptosis in chronic lymphocytic leukemia cells: mechanistic studies of Smac mimetic.Oncotarget · 2016Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
A growing body of evidence suggests that the resistance of CLL cells to apoptosis is partly mediated through the interactions between leukemia cells and adjacent stromal cells residing in the lymphatic tissue or bone marrow microenvironment. Mcl-1, an anti-apoptotic protein that is associated with failure to treatment is up-regulated in CLL lymphocytes after interaction with microenvironment. However, the regulation of its expression in context to microenvironment is unclear. We evaluated and compared changes in Mcl-1 in CLL B-cells in suspension culture and when co-cultured on stromal cells. The blockade of apoptosis in co-cultured CLL cells is associated with diminution in caspase-3 and PARP cleavage and is not dependent on cytogenetic profile or prognostic factors of the disease. Stroma-derived resistance to apoptosis is associated with a cascade of transcriptional events such as increase in levels of total RNA Pol II and its phosphorylation at Ser2 and Ser5, increase in the rate of global RNA synthesis, and amplification of Mcl-1 transcript levels. The latter is associated with increase in Mcl-1 protein level without an impact on the levels of Bcl-2 and Bcl-xL. Post-translational modifications of protein kinases show increased phosphorylation of Akt at Ser473, Erk at Thr202/Tyr204 and Gsk-3β at Ser9 and augmentation of total Mcl-1 accumulation along with phosphorylation at Ser159/Thr163 sites. Collectively, stroma-induced apoptosis resistance is mediated through signaling proteins that regulate transcriptional and translational expression and post-translational modification of Mcl-1 in CLL cells in context to bone marrow stromal microenvironment.
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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.