Leukemia Propagating Cells Rebuild an Evolving Niche in Response to Therapy
Open accessAbstract
Residence of cancer-propagating cells (CPCs) within preferential microenvironmental niches has a major part in evading therapy. However, the nature of niches involved and the mechanisms protecting CPCs remain largely unknown. We addressed these issues in mouse transplantation models of acute lymphoblastic leukemia (ALL). When the engrafted leukemic cells substantially damaged adjacent microenvironment in the bone marrow (BM), after chemotherapy small foci of CPCs were retained, surrounded by sheaths of supporting cells that comprise a protective niche. We investigated patients' BM biopsies and found evidence of a similar process in patients receiving induction therapy. The efficacy of chemotherapy was enhanced by interfering with the niche formation or function. We therefore identified a therapy-induced niche that protects CPCs.
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These altered cells are difficult to eliminate by conventional antitumoral agents because drugs do not reach the bone marrow at the required concentration, and because the stem cell niche changes/adapts after chemotherapy, protecting altered cells.
“These altered cells are difficult to eliminate by conventional antitumoral agents because drugs do not reach the bone marrow at the required concentration, and because the stem cell niche (a physical and functional entity that supports the self-renewal and differentiation of stem cells) changes/adapts after chemotherapy, protecting altered cells97.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [97]
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- Authors
- Duan, C.-W., Shi, J., Chen, J., Wang, B., Yu, Y.-H., Qin, X., Zhou, X.-C., Cai, Y.-J., Li, Z.-Q., Zhang, F., Yin, M.-Z., Tao, Y., Mi, J.-Q., Li, L.-H., Enver, T., Chen, G.-Q., & Hong, D.-L.
- Affiliations
- Shanghai Jiao Tong University (CN)
- University College London (GB)
- Corresponding author
- Enver, Tariq
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 25
- Issue
- 6
- Pages
- 778-793
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2094470615
- Cited by
- 198
- References
- 36
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 9 · 2023: 18 · 2022: 16 · 2021: 16 · 2020: 17 · 2019: 13 · 2018: 30 · 2017: 22 · 2016: 16 · 2015: 18 · 2014: 5
- FWCI
- 20.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Cancer Research UK (12796)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- acute lymphoblastic leukemia, leukemia microenvironment, bone marrow microenvironment, chemoresistance, niche formation, supporting cells, induction therapy, mouse transplantation model
- MeSH terms
- Animals, Antineoplastic Combined Chemotherapy Protocols, Biopsy, Bone Marrow Cells, Cytarabine, Daunorubicin, Disease Models, Animal, Humans, Neoplastic Stem Cells, Mice, SCID, Mice, Inbred NOD, Xenograft Model Antitumor Assays, Mice, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Stem Cell Niche, Tumor Microenvironment
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