ArticleLeukemia & lymphoma2011
Activation of CD44, a receptor for extracellular matrix components, protects chronic lymphocytic leukemia cells from spontaneous and drug induced apoptosis through MCL-1.
Article in Leukemia & lymphoma, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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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
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- A Systematic Review to Clarify the Prognostic Values of CD44 and CD44Frontiers in oncology · 2021Pooled it
- Revitalizing Muscle Repair: Hyaluronan Preserves Mitochondrial Architecture and Promotes Myogenesis Under Pro-Inflammatory Conditions.Biomolecules · 2026Article
- A 3D lymph node model for chronic lymphocytic leukaemia recapitulates microenvironmental features and drug response in vitro.Disease models & mechanisms · 2026Article
- Defining PI3K Signaling as a Key Regulator of Molecular Heterogeneity and Inflammation in Glomerular Lupus Nephritis.Immune network · 2026Article
- Extracellular matrix mediates circulating tumor cell clustering in triple-negative breast cancer metastasis.Nature communications · 2026Article
- Notch2, a Key Player in Chronic Lymphocytic Leukemia: Mechanism, Microenvironment Interactions, and Therapeutic Implications.Cancers · 2026Review
- CD44 and phosphorylated ERK1/2 coexpression predicts distant metastasis in colorectal cancer based on a study of 1137 Saudi patients.Scientific reports · 2025Article
- Impact of Symptomatic Slow-Acting Drugs on Inflammatory Pathways in Osteoarthritis: Therapeutic Advances and Future Challenges.ACS pharmacology & translational science · 2025Review
- PI3 K/AKT/mTOR pathway and its role in breast cancer stem cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- CD44 as a Central Integrator of Inflammation and Fibrosis: From Molecular Signaling to Environmental Modulation.International journal of molecular sciences · 2025Review
- A translational perspective of the malignant hematopoietic proteoglycome.Cell & bioscience · 2025Review
- Exosomal miR-6126 as a novel therapeutic target for overcoming resistance of anti-cancer effect in hepatocellular carcinoma.BMC cancer · 2024Article
- Strain and hyaluronic acid interact to regulate ovarian cancer cell proliferation, migration, and drug resistance.Mechanobiology in medicine · 2024Article
- CD44 signaling in Müller cells impacts photoreceptor function and survival in healthy and diseased retinas.Journal of neuroinflammation · 2024Article
- Potential New Therapies "ROS-Based" in CLL: An Innovative Paradigm in the Induction of Tumor Cell Apoptosis.Antioxidants (Basel, Switzerland) · 2024Review
- Downregulation of LAMB3 Altered the Carcinogenic Properties of Human Papillomavirus 16-Positive Cervical Cancer Cells.International journal of molecular sciences · 2024Article
- Deciphering the evolving niche interactome of human hematopoietic stem cells from ontogeny to aging.Frontiers in molecular biosciences · 2024Article
- Cluster of differentiation-44 as a novel biomarker of lupus nephritis and its role in kidney inflammation and fibrosis.Frontiers in immunology · 2024Article
- Identification of genes associated with gall bladder cell carcinogenesis: Implications in targeted therapy of gall bladder cancer.World journal of gastrointestinal oncology · 2023Review
- The Hyaluronan/CD44 Axis: A Double-Edged Sword in Cancer.International journal of molecular sciences · 2023Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Survival of chronic lymphocytic leukemia (CLL) cells in vivo is supported by the tissue microenvironment, which includes components of the extracellular matrix. Interactions between tumor cells and the extracellular matrix are in part mediated by CD44, whose principal ligand is hyaluronic acid. Here, we show that CD44 is more highly expressed on CLL cells of the clinically more progressive immunglobulin heavy chain variable gene (IGHV)-unmutated subtype than on cells of the IGHV-mutated type. Engagement of CD44 activated the phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen activated protein kinase (MAPK)/ERK pathways and increased myeloid cell leukemia sequence 1 (MCL-1) protein expression. Consistent with the induction of these anti-apoptotic mechanisms, CD44 protected CLL cells from spontaneous and fludarabine-induced apoptosis. Obatoclax, an antagonist of MCL-1, blocked the pro-survival effect of CD44. In addition, obatoclax synergized with fludarabine to induce apoptosis of CLL cells. In conclusion, components of the extracellular matrix may provide survival signals to CLL cells through engagement of CD44. Inhibition of MCL-1 is a promising strategy to reduce the anti-apoptotic effect of the microenvironment on CLL cells.
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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.