ArticleHaematologica2021
CD44 engagement enhances acute myeloid leukemia cell adhesion to the bone marrow microenvironment by increasing VLA-4 avidity.
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Extracellular cyclophilin A promotes B-cell acute lymphoblastic leukemia progression via MC2R.EMBO molecular medicine · 2026Article
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- eIF4E and Ezrin cooperate in pseudopods to drive a localized migratory translation program in acute myeloid leukemia.bioRxiv : the preprint server for biology · 2026Article
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- Exploring the Bone Marrow Microenvironment as a Therapeutic Barrier and Targetable Source of Crosstalk in Acute Myeloid Leukemia.Blood and lymphatic cancer : targets and therapy · 2026Review
- Article
- Sonidegib Inhibits the Adhesion of Acute Myeloid Leukemia to the Bone Marrow in Hypoxia: An Optical Tweezer Study.Biomedicines · 2025Article
- A translational perspective of the malignant hematopoietic proteoglycome.Cell & bioscience · 2025Review
- Review
- Article
- Flow cytometric detection of leukemic stem cells in Acute Myeloid Leukemia: current status and future directions.Frontiers in pharmacology · 2025Review
- Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.Molecular cancer · 2024Review
- Biology and Therapeutic Properties of Mesenchymal Stem Cells in Leukemia.International journal of molecular sciences · 2024Review
- CD44: a cancer stem cell marker and therapeutic target in leukemia treatment.Frontiers in immunology · 2024Review
- Understanding the interaction between leukaemia stem cells and their microenvironment to improve therapeutic approaches.British journal of pharmacology · 2024Review
- The characteristics and the multiple functions of integrin β1 in human cancers.Journal of translational medicine · 2023Review
- The Molecular Context of Oxidant Stress Response in Cancer Establishes ALDH1A1 as a Critical Target: What This Means for Acute Myeloid Leukemia.International journal of molecular sciences · 2023Review
- A potential area of use for immune checkpoint inhibitors: Targeting bone marrow microenvironment in acute myeloid leukemia.Frontiers in immunology · 2023Review
- The biology of E-selectin ligands in leukemogenesis.Advances in cancer research · 2023Review
- A novel ferroptosis-related gene signature can predict prognosis and influence immune microenvironment in acute myeloid leukemia.Bosnian journal of basic medical sciences · 2022Article
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 4 countries.
Funding
Abstract
Adhesive properties of leukemia cells shape the degree of organ infiltration and the extent of leukocytosis. CD44 and the integrin VLA-4, a CD49d/CD29 heterodimer, are important factors of progenitor cell adhesion in bone marrow (BM). Here, we report their cooperation in acute myeloid leukemia (AML) by a novel non-classical CD44-mediated way of inside-out VLA-4 activation. In primary AML BM samples from patients and the OCI-AML3 cell line, CD44 engagement by hyaluronan induced inside-out activation of VLA-4 resulting in enhanced leukemia cell adhesion on VCAM-1. This was independent from VLA-4 affinity regulation but based on ligand-induced integrin clustering on the cell surface. CD44-induced VLA-4 activation could be inhibited by the Src family kinase inhibitor PP2 and the multikinase inhibitor midostaurin. In further consequence, the increased adhesion on VCAM-1 allowed AML cells to strongly bind stromal cells. Thereby VLA-4/VCAM-1 interaction promoted activation of Akt, MAPK, NF-kB and mTOR signaling and decreased AML cell apoptosis. Collectively, our investigations provide a mechanistic description of an unusual CD44 function in regulating VLA-4 avidity in AML, supporting AML cell retention in the supportive BM microenvironment.
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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.