ArticleLeukemia2012
Role of stromal microenvironment in nonpharmacological resistance of CML to imatinib through Lyn/CXCR4 interactions in lipid rafts.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Biology and Therapeutic Properties of Mesenchymal Stem Cells in Leukemia.International journal of molecular sciences · 2024Review
- Fluorescent Detection of Peroxynitrite Produced by Myeloid-Derived Suppressor Cells in Cancer and Inhibition by Dasatinib.ACS pharmacology & translational science · 2023Article
- TIAR and FMRP shape pro-survival nascent proteome of leukemia cells in the bone marrow microenvironment.iScience · 2023Article
- BCR-ABL1-driven exosome-miR130b-3p-mediated gap-junction Cx43 MSC intercellular communications imply therapies of leukemic subclonal evolution.Theranostics · 2023Article
- Cancer non-stem cells as a potent regulator of tumor microenvironment: a lesson from chronic myeloid leukemia.Molecular biomedicine · 2021Review
- Extracellular Adenine Nucleotides and Adenosine Modulate the Growth and Survival of THP-1 Leukemia Cells.International journal of molecular sciences · 2020Article
- Article
- Exosomes from Bone Marrow Microenvironment-Derived Mesenchymal Stem Cells Affect CML Cells Growth and Promote Drug Resistance to Tyrosine Kinase Inhibitors.Stem cells international · 2020Article
- Bone marrow-derived mesenchymal stromal cells promote resistance to tyrosine kinase inhibitors in chronic myeloid leukemia via the IL-7/JAK1/STAT5 pathway.The Journal of biological chemistry · 2019Article
- Stem cell persistence in CML is mediated by extrinsically activated JAK1-STAT3 signaling.Leukemia · 2019Article
- BETP degradation simultaneously targets acute myelogenous leukemia stem cells and the microenvironment.The Journal of clinical investigation · 2019Article
- [Bone marrow mesenchymal stromal cells mediated drug resistance in hematological malignancies].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2018Article
- Cell adhesion-mediated mitochondria transfer contributes to mesenchymal stem cell-induced chemoresistance on T cell acute lymphoblastic leukemia cells.Journal of hematology & oncology · 2018Article
- Combined targeting of STAT3 and STAT5: a novel approach to overcome drug resistance in chronic myeloid leukemia.Haematologica · 2017Article
- Chemokines as a Conductor of Bone Marrow Microenvironment in Chronic Myeloid Leukemia.International journal of molecular sciences · 2017Review
- Myeloid malignancies and the microenvironment.Blood · 2017Article
- Cellular and Molecular Networks in Chronic Myeloid Leukemia: The Leukemic Stem, Progenitor and Stromal Cell Interplay.Current drug targets · 2017Review
- Article
- Essential Role of Lyn in Fibrosis.Frontiers in physiology · 2016Article
- Directed Evolution of a Highly Specific FN3 Monobody to the SH3 Domain of Human Lyn Tyrosine Kinase.PloS one · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
We and others have previously demonstrated that p210 Bcr-Abl tyrosine kinase inhibits stromal cell-derived factor-1α/CXCR4 chemokine receptor signaling, contributing to the deficient adhesion of chronic myeloid leukemia (CML) cells to bone marrow stroma. Conversely, exposure of CML cells to a tyrosine kinase inhibitor (TKI) enhances migration of CML cells towards stromal cell layers and promotes non-pharmacological resistance to imatinib. Src-related kinase Lyn is known to interact with CXCL12/CXCR4 signaling and is directly activated by p210 Bcr-Abl. In this study, we demonstrate that TKI treatment promoted CXCR4 redistribution into the lipid raft fraction, in which it co-localized with active phosphorylated form of Lyn (LynTyr396) in CML cells. Lyn inhibition or cholesterol depletion abrogated imatinib-induced migration, and dual Src/Abl kinase inhibitor dasatinib induced fewer CML cells to migrate to the stroma. These findings demonstrate the novel mechanism of microenvironment-mediated resistance through lipid raft modulation, which involves compartmental changes of the multivalent CXCR4 and Lyn complex. We propose that pharmacological targeting of lipid rafts may eliminate bone marrow-resident CML cells through interference with microenvironment-mediated resistance.
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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.