Title |
Telomerase Inhibition Effectively Targets Mouse and Human AML Stem Cells and Delays Relapse following Chemotherapy
|
---|---|
Published in |
Cell Stem Cell, December 2014
|
DOI | 10.1016/j.stem.2014.11.010 |
Pubmed ID | |
Authors |
Claudia Bruedigam, Frederik O. Bagger, Florian H. Heidel, Catherine Paine Kuhn, Solene Guignes, Axia Song, Rebecca Austin, Therese Vu, Erwin Lee, Sarbjit Riyat, Andrew S. Moore, Richard B. Lock, Lars Bullinger, Geoffrey R. Hill, Scott A. Armstrong, David A. Williams, Steven W. Lane |
Abstract |
Acute myeloid leukemia (AML) is an aggressive and lethal blood cancer maintained by rare populations of leukemia stem cells (LSCs). Selective targeting of LSCs is a promising approach for treating AML and preventing relapse following chemotherapy, and developing such therapeutic modalities is a key priority. Here, we show that targeting telomerase activity eradicates AML LSCs. Genetic deletion of the telomerase subunit Terc in a retroviral mouse AML model induces cell-cycle arrest and apoptosis of LSCs, and depletion of telomerase-deficient LSCs is partially rescued by p53 knockdown. Murine Terc(-/-) LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia progression, and delays relapse following chemotherapy. Altogether, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 4 | 29% |
Canada | 1 | 7% |
Unknown | 9 | 64% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 11 | 79% |
Science communicators (journalists, bloggers, editors) | 2 | 14% |
Scientists | 1 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
India | 2 | 2% |
Austria | 2 | 2% |
Netherlands | 1 | 1% |
Australia | 1 | 1% |
United Kingdom | 1 | 1% |
Unknown | 88 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 24 | 25% |
Student > Ph. D. Student | 22 | 23% |
Student > Bachelor | 13 | 14% |
Student > Master | 8 | 8% |
Other | 3 | 3% |
Other | 14 | 15% |
Unknown | 11 | 12% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 29 | 31% |
Agricultural and Biological Sciences | 28 | 29% |
Medicine and Dentistry | 15 | 16% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 2% |
Arts and Humanities | 1 | 1% |
Other | 4 | 4% |
Unknown | 16 | 17% |