Journal
NATURE REVIEWS IMMUNOLOGY
Volume 10, Issue 3, Pages 201-209Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nri2726
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Funding
- European Union
- German 'Bundesministerium fur Bildung und Forschung' (BMBF)
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Haematopoietic stem cells (HSCs) in mouse bone marrow are located in specialized niches as single cells. During homeostasis, signals from this environment keep some HSCs dormant, which preserves long-term self-renewal potential, while other HSCs actively self renew to maintain haematopoiesis. In response to haematopoietic stress, dormant HSCs become activated and rapidly replenish the haematopoietic system. Interestingly, three factors-granulocyte colony-stimulating factor, interferon-alpha and arsenic trioxide-have been shown to efficiently activate dormant stem cells and thereby could break their resistance to anti-proliferative chemotherapeutics. Thus, we propose that two-step strategies could target resistant leukaemic stem cells by priming tumours with activators of dormancy followed by chemotherapy or targeted therapies.
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