ArticleJournal of experimental & clinical cancer research : CR2018
Chemotherapy-induced niche perturbs hematopoietic reconstitution in B-cell acute lymphoblastic leukemia.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
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- Interleukin-27 remodels the bone marrow niche to suppress B-cell development and leukaemia progression in mouse models.EBioMedicine · 2026Article
- Dying cells as architects of the stem cell niche: a conserved mechanism driving tissue regeneration and tumor therapy resistance.Cell communication and signaling : CCS · 2026Review
- Oral ulcers in hematological malignancy patients undergoing chemotherapy: is it chemotherapy or neutropenia?: a case report and review of the literature.Journal of medical case reports · 2025Review
- Article
- Osteoimmunology in bone malignancies: a symphony with evil.Journal of the National Cancer Center · 2024Review
- Mechanobiology and Primary Cilium in the Pathophysiology of Bone Marrow Myeloproliferative Diseases.International journal of molecular sciences · 2024Review
- Oxidative stress is two-sided in the treatment of acute myeloid leukemia.Cancer medicine · 2024Review
- Selected stem cell populations in pediatric acute lymphoblastic leukemia.Frontiers in immunology · 2024Article
- DEX-Induced SREBF1 Promotes BMSCs Differentiation into Adipocytes to Attract and Protect Residual T-Cell Acute Lymphoblastic Leukemia Cells After Chemotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Cytogenetic culture failure and its causes in hematological disorders; a single centre perspective.Molecular cytogenetics · 2023Article
- Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?Antioxidants (Basel, Switzerland) · 2022Review
- The immune checkpoint ICOSLG is a relapse-predicting biomarker and therapeutic target in infant t(4;11) acute lymphoblastic leukemia.iScience · 2022Article
- Reactive Oxygen Species in Acute Lymphoblastic Leukaemia: Reducing Radicals to Refine Responses.Antioxidants (Basel, Switzerland) · 2021Review
- Redox Control in Acute Lymphoblastic Leukemia: From Physiology to Pathology and Therapeutic Opportunities.Cells · 2021Review
- The Immunomodulatory Properties of Mesenchymal Stem Cells Play a Critical Role in Inducing Immune Tolerance after Liver Transplantation.Stem cells international · 2021Review
- Mechanoregulation in hematopoiesis and hematologic disorders.Current stem cell reports · 2020Article
- Oxidative resistance of leukemic stem cells and oxidative damage to hematopoietic stem cells under pro-oxidative therapy.Cell death & disease · 2020Review
- Therapy-related acute myeloid leukemia and its prevention.American journal of blood research · 2020Review
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundConsiderable efforts have been devoted toward the uncovering of the molecular mechanisms underlying the maintenance of hematopoietic stem cells (HSCs) by the normal bone marrow (BM) niche. Previously, we demonstrated that a chemotherapy-induced niche, which is mainly composed of mesenchymal stem cells (MSCs), protects the residual B-cell acute lymphoblastic leukemia (B-ALL) cells from the insult of chemotherapeutic drugs. However, the roles of chemotherapy-induced niche on HSCs functions in B-ALL remain unclear.
methodsWe established an oncogenic N-MYC-driven B-ALL mouse model, which were subsequently treated with common chemotherapy drug cytarabine (Ara-C) and daunorubicin (DNR). After treatment, the structures of the BM niche were imaged by immunofluorescence staining. Then, the self-renewal and differentiation capability of the MSCs in the BM after Ara-C and DNR treatment were studied by ex vivo culture and gene expression analysis with RNA-seq and qRT-PCR. The effects of chemotherapy-induced niche on the hematopoietic reconstitution of HSCs were determined with series transplantation assay. Furthermore, the cell cycle, ROS level, mitochondrial membrane potential and cell apoptosis of HSCs were detected by flow cytometry.
resultsThe MSCs, which is the main component of chemotherapy-induced BM niche, have decreased self-renewal capability and are prone to differentiate into adipocytes and chondrocytes. The results of gene expression analysis with RNA-seq showed that the MSCs have reduced levels of cytokines, including SCF, CXCL12, ANGPT1, VCAM1, and IL7. Furthermore, the chemotherapy-induced niche perturbed the hematopoietic reconstitution of HSCs in our N-MYC-driven B-ALL mouse model by promoting HSCs to enter cell cycle and increasing intracellular ROS levels and mitochondrial membrane potential of HSCs, which lead to the cell apoptosis of HSCs.
conclusionsChemotherapy-induced BM niche perturbs the hematopoietic reconstitution of HSCs by increasing intracellular ROS level and inducing cell apoptosis.
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