ArticleJournal of clinical medicine2022
Imetelstat Induces Leukemia Stem Cell Death in Pediatric Acute Myeloid Leukemia Patient-Derived Xenografts.
Article in Journal of clinical medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- No Effect of Immunogenicity on Pharmacokinetics, Efficacy, and Safety of the Oligonucleotide Telomerase Inhibitor Imetelstat in Lower-Risk Myelodysplastic Syndromes.Clinical and translational science · 2025Trial
- FDA approval of imetelstat: a new era in the treatment of lower-risk myelodysplastic syndrome.Annals of medicine and surgery (2012) · 2025Review
- The interplay of DNA damage, epigenetics and tumour heterogeneity in driving cancer cell fitness.Nature communications · 2025Review
- Perspectives on the origin and therapeutic opportunities in Down syndrome-associated leukemia.Cancer metastasis reviews · 2025Review
- Canonical and non-canonical functions of the non-coding RNA component (TERC) of telomerase complex.Cell & bioscience · 2025Review
- Recent progress in human telomerase structure and its therapeutic targeting.Frontiers in molecular biosciences · 2025Review
- Imetelstat, a novel, first-in-class telomerase inhibitor: Mechanism of action, clinical, and translational science.Clinical and translational science · 2024Review
- Imetelstat: First Approval.Drugs · 2024Review
- Ferroptosis: principles and significance in health and disease.Journal of hematology & oncology · 2024Review
- The regulations of telomerase reverse transcriptase (TERT) in cancer.Cell death & disease · 2024Review
- Emerging and Future Targeted Therapies for Pediatric Acute Myeloid Leukemia: Targeting the Leukemia Stem Cells.Biomedicines · 2023Review
- Bone Marrow Microenvironment-Induced Chemoprotection inCancers · 2023Article
- The Relevance of Telomerase and Telomere-Associated Proteins in B-Acute Lymphoblastic Leukemia.Genes · 2023Review
- Consecutive Inhibition of Telomerase and Alternative Lengthening Pathway Promotes Hodgkin's Lymphoma Cell Death.Biomedicines · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Acute myeloid leukemia (AML) in children remains deadly, despite the use of maximally intensive therapy. Because leukemia stem cells (LSCs) significantly contribute to chemoresistance and relapse, therapies that specifically target the LSCs are likely to be more beneficial in improving outcome. LSCs are known to have high telomerase activity and telomerase activity is negatively correlated with survival in pediatric AML. We evaluated the preclinical efficacy of imetelstat, an oligonucleotide inhibitor of telomerase activity in patient-derived xenograft (PDX) lines of pediatric AML. Imetelstat treatment significantly increased apoptosis/death of the LSC population in a dose-dependent manner in six pediatric AML PDX lines ex vivo, while it had limited activity on the stem cell population in normal bone marrow specimens. These results were validated in vivo in two distinct PDX models wherein imetelstat as single agent or in combination with chemotherapy greatly reduced the LSC percentage and prolonged median survival. Imetelstat combination with DNA hypomethylating agent azacitidine was also beneficial in extending survival. Secondary transplantation experiments showed delayed engraftment and improved survival of mice receiving imetelstat-treated cells, confirming the diminished LSC population. Thus, our data suggest that imetelstat represents an effective therapeutic strategy for pediatric AML.
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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.