ArticleThe Journal of experimental medicine2014
Niche displacement of human leukemic stem cells uniquely allows their competitive replacement with healthy HSPCs.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 89 citations in OpenAlex.
- MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway.Experimental hematology & oncology · 2025Article
- TIM-3 marks measurable residual leukemic stem cells responsible for relapse after allogeneic stem cell transplantation.Cancer science · 2025Article
- CCR2 cooperativity promotes hematopoietic stem cell homing to the bone marrow.Science advances · 2024Article
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- Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma.Biomolecules · 2023Review
- Reprogramming of Acute Myeloid Leukemia Patients Cells: Harboring Cancer Mutations Requires Targeting of AML Hierarchy.Stem cells translational medicine · 2023Article
- HSC Niche Dynamics in Regeneration, Pre-malignancy, and Cancer: Insights From Mathematical Modeling.Stem cells (Dayton, Ohio) · 2023Article
- Targeting the Retinoic Acid Pathway to Eradicate Cancer Stem Cells.International journal of molecular sciences · 2023Review
- Targeting CAM-DR and Mitochondrial Transfer for the Treatment of Multiple Myeloma.Current oncology (Toronto, Ont.) · 2022Review
- The immune checkpoint ICOSLG is a relapse-predicting biomarker and therapeutic target in infant t(4;11) acute lymphoblastic leukemia.iScience · 2022Article
- Article
- The Social Norm of Hematopoietic Stem Cells and Dysregulation in Leukemia.International journal of molecular sciences · 2022Review
- Niche-directed therapy in acute myeloid leukemia: optimization of stem cell competition for niche occupancy.Leukemia & lymphoma · 2022Review
- Nestin-GFP transgene labels immunoprivileged bone marrow mesenchymal stem cells in the model of ectopic foci formation.Frontiers in cell and developmental biology · 2022Article
- Regulation of Malignant Myeloid Leukemia by Mesenchymal Stem Cells.Frontiers in cell and developmental biology · 2022Review
- Review
- The Role of Hypoxic Bone Marrow Microenvironment in Acute Myeloid Leukemia and Future Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- Abnormal dopamine receptor signaling allows selective therapeutic targeting of neoplastic progenitors in AML patients.Cell reports. Medicine · 2021Article
- Remodeling of Bone Marrow Niches and Roles of Exosomes in Leukemia.International journal of molecular sciences · 2021Review
- Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Allogeneic hematopoietic stem cell (HSC) transplantation (HSCT) is currently the leading strategy to manage acute myeloid leukemia (AML). However, treatment-related morbidity limits the patient generalizability of HSCT use, and the survival of leukemic stem cells (LSCs) within protective areas of the bone marrow (BM) continues to lead to high relapse rates. Despite growing appreciation for the significance of the LSC microenvironment, it has remained unresolved whether LSCs preferentially situate within normal HSC niches or whether their niche requirements are more promiscuous. Here, we provide functional evidence that the spatial localization of phenotypically primitive human AML cells is restricted to niche elements shared with their normal counterparts, and that their intrinsic ability to initiate and retain occupancy of these niches can be rivaled by healthy hematopoietic stem and progenitor cells (HSPCs). When challenged in competitive BM repopulation assays, primary human leukemia-initiating cells (L-ICs) can be consistently outperformed by HSPCs for BM niche occupancy in a cell dose-dependent manner that ultimately compromises long-term L-IC renewal and subsequent leukemia-initiating capacity. The effectiveness of this approach could be demonstrated using cytokine-induced mobilization of established leukemia from the BM that facilitated the replacement of BM niches with transplanted HSPCs. These findings identify a functional vulnerability of primitive leukemia cells, and suggest that clinical development of these novel transplantation techniques should focus on the dissociation of L-IC-niche interactions to improve competitive replacement with healthy HSPCs during HSCT toward increased survival of patients.
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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.