ArticleHaematologica2010
The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces apoptosis, down-regulates the CXCR4 chemokine receptor and impairs migration of chronic lymphocytic leukemia cells.
Article in Haematologica, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Chemokine-chemokine receptor axis: Emerging immunotherapeutic paradigms for solid tumor microenvironment reprogramming.Chinese medical journal · 2026Review
- Tumor microenvironment as a novel therapeutic target for lymphoid leukemias.Annals of hematology · 2025Review
- The current status of anti-GPCR drugs against different cancers.Journal of pharmaceutical analysis · 2020Review
- Importance of Crosstalk Between Chronic Lymphocytic Leukemia Cells and the Stromal Microenvironment: Direct Contact, Soluble Factors, and Extracellular Vesicles.Frontiers in oncology · 2020Review
- Histone modifier gene mutations in peripheral T-cell lymphoma not otherwise specified.Haematologica · 2018Article
- The role of G protein-coupled receptors in lymphoid malignancies.Cellular signalling · 2017Review
- Suppression of chronic lymphocytic leukemia progression by CXCR4 inhibitor WZ811.American journal of translational research · 2016Article
- Effective elimination of chronic lymphocytic leukemia cells in the stromal microenvironment by a novel drug combination strategy using redox-mediated mechanisms.Molecular medicine reports · 2015Article
- Plerixafor as a chemosensitizing agent in pediatric acute lymphoblastic leukemia: efficacy and potential mechanisms of resistance to CXCR4 inhibition.Oncotarget · 2014Article
- Article
- The gene signature in CCAAT-enhancer-binding protein α dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors.Haematologica · 2014Article
- Dynamic chemotherapy-induced upregulation of CXCR4 expression: a mechanism of therapeutic resistance in pediatric AML.Molecular cancer research : MCR · 2013Article
- Histone deacetylase inhibitors induce CXCR4 mRNA but antagonize CXCR4 migration.Cancer biology & therapy · 2013Article
- HDAC isoenzyme expression is deregulated in chronic lymphocytic leukemia B-cells and has a complex prognostic significance.Epigenetics · 2012Article
- Article
- The bone marrow microenvironment and leukemia: biology and therapeutic targeting.Expert review of hematology · 2011Review
- Treatment options for high-risk chronic lymphocytic leukaemia.Therapeutic advances in hematology · 2011Article
- Nuclear protein isoforms: implications for cancer diagnosis and therapy.Journal of cellular biochemistry · 2011Review
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6 authors.
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Abstract
backgroundChronic lymphocytic leukemia is a neoplastic disorder that arises largely as a result of defective apoptosis leading to chemoresistance. Stromal cell-derived factor-1 and its receptor, CXCR4, have been shown to play an important role in chronic lymphocytic leukemia cell trafficking and survival. DESIGN AND
methodsSince histone acetylation is involved in the modulation of gene expression, we evaluated the effects of suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, on chronic lymphocytic leukemia cells and in particular on cell survival, CXCR4 expression, migration, and drug sensitization.
resultsHere, we showed that treatment with suberoylanilide hydroxamic acid (20 microM) for 48 hours induced a decrease in chronic lymphocytic leukemia cell viability via apoptosis (n=20, P=0.0032). Using specific caspase inhibitors, we demonstrated the participation of caspases-3, -6 and -8, suggesting an activation of the extrinsic pathway. Additionally, suberoylanilide hydroxamic acid significantly decreased CXCR4 mRNA (n=10, P=0.0010) and protein expression (n=40, P<0.0001). As a result, chronic lymphocytic leukemia cell migration in response to stromal cell-derived factor-1 (n=23, P<0.0001) or through bone marrow stromal cells was dramatically impaired. Consequently, suberoylanilide hydroxamic acid reduced the protective effect of the microenvironment and thus sensitized chronic lymphocytic leukemia cells to chemotherapy such as fludarabine.
conclusionsIn conclusion, suberoylanilide hydroxamic acid induces apoptosis in chronic lymphocytic leukemia cells via the extrinsic pathway and down-regulates CXCR4 expression leading to decreased cell migration. Suberoylanilide hydroxamic acid in combination with other drugs represents a promising therapeutic approach to inhibiting migration, chronic lymphocytic leukemia cell survival and potentially overcoming drug resistance.
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